Saturday, June 22, 2019, from 3:30pm to 5:30pm
P3.1 LC-MS/MS PROFILING OF SYSTEMIC AND BRAIN STEROID LEVELS IN A SONGBIRD
Cecilia Jalabert1, Chunqi Ma2, Kiran K. Soma1,2,3
Department of 1Zoology and 2Psychology and 3Djavad Mowafaghian Centre for Brain Health | The University of British Columbia, Canada
In some species, territorial aggression is expressed in the non-breeding season, when the gonads are regressed and circulating levels of sex steroids are very low. In such species, brain-derived steroids (“neurosteroids”) might promote non-breeding aggression. Here, in wild territorial male song sparrows, we measured steroids using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a cutting-edge technique that is highly specific and sensitive and allows simultaneous measurement of multiple analytes. We examined a panel of 10 steroids: pregnenolone, progesterone, corticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone (5α-DHT), 17β-estradiol (E2), 17α-estradiol, and estrone. We explored seasonal changes in steroids in the blood and in 10 microdissected brain regions that regulate social behavior. As expected, systemic androgen levels were higher in the breeding season. Furthermore, in the breeding season, 5α-DHT levels were 20-fold higher in specific regions than in blood. In addition, E2 and estrone were detectable in the brain but not in the blood. In breeding and non-breeding seasons, progesterone varied across brain regions, despite similar levels in the circulation. Taken together, these results indicate that steroid levels are locally regulated within the brain and are not a simple reflection of levels in the circulation. For the first time in songbirds, we measured a panel of bioactive sex steroids and their precursors with great spatial resolution in the brain and obtained a clearer picture of natural neuroendocrine fluctuations in wild animals. These data suggest that steroid profiling by LC-MS/MS will be broadly useful and open the door for a new era of comparative neuroendocrinology.
P3.2 INJECTIONS OF A V1aR ANTAGONIST INTO THE DORSAL RAPHE AND LATERAL HABENULA ALTER COMMUNICATION IN MALE MICE
Nicole Rigney, Rachael Beaumont, Aras Petrulis
Neuroscience Institute | Georgia State University USA
The neuropeptide arginine-vasopressin (AVP) has long been implicated in the regulation of social behavior and communication in diverse taxa, often through its actions on the V1a receptor (V1aR) and in a sex-different and steroid-dependent way. One source of sex-different brain AVP is the steroid-sensitive and sexually-dimorphic AVP neurons in the bed nucleus of the stria terminalis (BNST). Indeed, we have demonstrated that these BNST-AVP neurons regulate social behavior in a sex-dependent manner. Potential targets of these BNST-AVP cells include the dorsal raphe (DR) and lateral habenula (LHb), areas known to be important for social behavior, yet few studies have investigated AVP action within these regions. Consequently, to test if V1aR action in the DR or LHb control social behavior in a sexually dimorphic manner, we administered a highly-specific V1aR antagonist (or saline vehicle) in the DR and LHb of C57BL/6 male mice and tested its effects on social investigation, social communication (urine marking, ultrasonic vocalizations (USV)), and territorial aggression. Preliminary results indicate that injecting the V1aR antagonist into the DR changed the repertoire of USV syllables produced toward females, whereas injecting it into the LHb reduced overall USV production. Additionally, V1aR antagonist injections into the DR increased investigation of male competitors and decreased urine marking toward males. Further work on DR/LHb in female mice will reveal if V1aR in the DR and LHb drive sex differences in social behavior and communication.
P3.3 INDEPENDENT AND INTERACTIVE EFFECTS OF SHORT-TERM ESTROGEN REPLACEMENT AND LONG-TERM PHYSICAL ACTIVITY POST MENOPAUSE ON BRAIN AND BEHAVIOR
Emily K. Oldridge, Tayyaba Masood, Daniel Phu, Justin V. Aickareth, J. Leigh Leasure, Shaefali P. Rodgers
Department of Psychology | University of Houston USA
We characterized the long-term, interactive effects of transient estrogen replacement (TER) and continuous physical activity (CPA) on brain and behavior in a rodent model of menopause. Middle-aged rats were ovariectomized and replaced with estradiol (E2) or vehicle (VEH) implants. Rats were placed in running wheels 2h/d for 5d/wk thereafter. However, wheels were locked for half the rats in each group. Implants were removed 6 wks after ovariectomy and 4 wks later behavior was assessed in an open field (OF), elevated plus maze (EPM), and Morris water maze (MWM). Voluntary wheel running was higher in E2 versus VEH runners and after implants were removed, although there was a significant decline in activity in E2 pre-exposed runners, they still ran twice as much as VEH pre-exposed runners, on average. All groups habituated to the OF although E2 pre-exposed rats travelled a greater distance relative to VEH pre-exposed rats. E2 pre-exposed rats spent more time in the open areas of the EPM and travelled a greater distance in the open arms than VEH pre-exposed rats. There were no differences between groups in spatial learning or memory in the MWM. However, E2 pre-exposed rats began to widen their search for the platform within the target quadrant after the first 30s of the probe trial, relative to VEH pre-exposed rats. Preliminary analyses indicate a TER x CPA effect on whole brain weight as well as hippocampal neurogenesis and neuroinflammation. Thus, postmenopausal neural and behavioral plasticity can be differentially modulated by mono- or combination-therapy approaches.
P3.4 ROLE OF ANDROGEN RECEPTORS DURING SEXUAL DIFFERENTIATION OF THE RAT BRAIN
Chaya Gopalan, Paige Niepoetter, Anil Cashikar
Southern Illinois University Edwardsville and Washington University School of Medicine Applied Health/Primary Care and Health Systems | Southern Illinois University Edwardsville USA
The brain differentiates into a female brain unless testosterone (T) is present during a critical window of time. In rats, there is a surge of T around the time of birth (perinatal period; PP). The purpose of this study was to examine the effects of blockade of androgen receptors (AR) during the PP using flutamide (F) on adult rat behaviors such as open field (OF), spatial working memory (SWM) and sexual motivation (SM) as well as the expression of AR and estrogen receptors (ER)-α and ER-β in the hippocampus, hypothalamus, and amygdala. Four timed-pregnant rats were divided into two groups: experimental group received F during PP whereas the control group received vehicle. Adult male rats underwent SM testing where they were exposed to an estrus and an ovariectomized rat. Both groups spent more time with the estrus rat suggesting that SM was not affected by AR blockade. Furthermore, male rats receiving F exhibited anxiety-like behavior. Spatial working memory test measured the amount of time spent in the arms with or without food. There was no significant difference in the time spent with food by either of the groups suggesting a lack of effect of AR in SWM. Reverse-phase PCR was carried out to quantify the levels of AR, ER-α, and ER-β in the hippocampus, hypothalamus, and amygdala using β-actin as an internal control. The expression of any of the receptors studied was not altered by the blockade of AR suggesting its limited role in causing anxiety-like behavior.
P3.5 GPER-1 ACTIVATION DIFFERENTIALLY ALTERS PREFERENCE FOR COCAINE IN MALE AND FEMALE RATS
Jacqueline A. Quigley, Jill B. Becker
Department of Psychology, Molecular and Behavioral Neuroscience Institute | University of Michigan USA
There are sex differences in susceptibility to addiction and drug-taking behaviors. A higher percentage of female rodents prefer cocaine to natural rewards than males do and females are more motivated than males to attain drugs of abuse. Research from the Becker Laboratory has shown that these heightened addiction-like behaviors in females are modulated by estradiol, where estradiol potentiates cocaine-induced dopamine levels in the dorsal striatum (dSTR). The role of estradiol, and other gonadal hormones, on addiction-like behaviors in males, however, is not well understood. The current experiment used ICI 182,780 (ICI) and G1 to manipulate estradiol receptors (ER) (ERα, ERß and GPER-1) in the dSTR. The first experiment used a conditioned place preference paradigm to determine whether ER manipulation alters preference for 10mg/kg cocaine in male or female rats. We found that treatment of ICI (ERα/ß antagonist and GPER-1 agonist) or G1 (GPER-1 agonist) into the dSTR of male rats blocks the preference for cocaine. Neither treatment alters female’s preference. These data suggest that GPER-1 regulates preference for cocaine in males only. The second experiment utilized qPCR to investigate GPER-1 expression within the dSTR between the sexes and found no difference. Together, these data suggest that GPER-1 activation decreases the rewarding effects of cocaine in males, but not females. Furthermore, it appears that there are sex differences in the effect of estradiol receptor activation on motivation for drugs of abuse: enhancing motivation in females while attenuating motivation in males.
P3.6 THE ROLE OF ANTIDEPRESSANTS ON ZEBRA FINCH PAIR BOND MAINTENANCE
Emily C. Fidlow, Lafayette College; Michelle L. Tomaszycki
Department of Psychology | Lafayette College USA
Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), are a highly prescribed drug. Yet, the exact neurobiological mechanisms, as well as its impacts on social relationships, are not well understood. A recent study found that, in female Eurasian starlings, exposure to ecologically relevant doses of fluoxetine (Prozac) reduced the amount of courtship behaviors they received by males, indicating that these females may have been considered less attractive as mates (Whitman et al., 2018). The aim of the present study was to test the effects of physiological SSRI dose on male and female courtship and pairing behavior in zebra finches. Eurasian starlings and zebra finches are closely related songbirds in which males perform courtship behaviors to a preferred female and the female chooses a mate based on those behaviors. I hypothesized that injecting fluoxetine weakens the strength of a previously established pair bond after a 48-hour separation period. I allowed pair bonds to form in mixed sex aviaries for two weeks then injected four birds of one sex with either one of two doses of fluoxetine (5mg/kg or 10mg/kg) dissolved in 0.9% sterile saline, or 0.9% sterile saline (control) into the pectoral muscle for three consecutive days. Pairs were then separated for 48 hours and the focal subject was tested in a 2-choice preference test. Following injections, males, but not females, exhibited significant differences in pair bonding behaviors. While in the 2-choice preference tests, both sexes exhibited a significant difference in time spent near their established mate.
P3.7 DO PRENATAL EDC EXPOSURES INCREASE VULNERABILITY OF PERIADOLESCENT FEMALE RATS TO MALE SEXUAL AGGRESSION?
Marcela Nicole Kunkel1, Morgan E. Hernandez2, Isabella Barnes1, Jennifer Gray1, Rachel Dixon1, Ximena de la Cruz1, Andrea C. Gore1,2,3
1Department of Psychology, 2Institute for Neuroscience, 3Division of Pharmacology & Toxicology | University of Texas at Austin USA
Endocrine-disrupting chemicals (EDCs) are ubiquitous in our environment. Prior work has shown that prenatal EDC exposures cause latent effects on brain development and behavior. Heightened stress reactivity during adolescence also produces lasting effects on adult phenotypes. However, the potential interaction of two such insults is unknown. Here, we tested whether prenatal EDCs altered the behaviors and stress reactivity in female rats exposed to vinclozolin (a fungicide), a PCB mixture, or vehicle (n=18) in utero from E8-18. From P35-41, females were given 30-minute sessions of either sexual conspecific aggressive response (SCAR) with a sexually-experienced adult male, or no exposure (n=9) every other day. One hour after their last SCAR, animals were euthanized (n=30). A one way ANOVA showed marginally significant EDC treatment effects on timing of vaginal opening (VO) (F2,48 = 2.993, p = 0.059). A bootstrap analysis of these data showed that the F value of the difference in VO timing across EDC treatment groups had a probability of occurring twice every hundred times (i.e., p ≈ 0.0248). A linear regression showed a significant relationship between VO timing and the number of mounts a female received across all SCAR sessions (F1,23 = 7.171, p = 0.0134). Thus, EDCs influence pubertal timing of female rats, which in turn influences how sexually experienced, adult male rats behave towards them during SCAR. Ongoing hormone assays and immunohistochemistry will provide additional insights into how prenatal and adolescent insults may interact in causing an adverse stress response.
P3.8 GLUCOCORTICOID PROFILING VIA LC-MS/MS IN BLOOD AND MICRODISSECTED BRAIN REGIONS: EFFECTS OF AN EARLY-LIFE STRESSOR
Katherine M. Gray, Jordan E. Hamden, Melody Salehzadeh, Cathy Ma, Kiran K. Soma
Behavioural Neuroscience | University of British Columbia Canada
Glucocorticoids (GCs) are steroids secreted by the adrenal glands and play critical roles in stress responses, immunity, and development. From post-natal day (PND) 2 to 12, mice show greatly decreased adrenal GC secretion at baseline and in response to stressors, termed the stress hyporesponsive period (SHRP). During the SHRP, baseline GC levels are higher in the brain than in the blood, suggesting local GC production. We hypothesized that the brain rapidly increases local GC production in response to an acute stressor. Here, we administered 5% isoflurane (an anesthetic and stressor) in oxygen, oxygen (vehicle control), or neither (baseline) to PND5 and PND13 mice. Mice were exposed to either isoflurane or oxygen for 3 min and euthanized at 30 min. Baseline animals were immediately euthanized after removal from the home cage. Using liquid chromatography tandem mass spectrometry (LC-MS/MS), we measured 7 steroids in blood, hypothalamus, cerebral cortex, and hippocampus with a high degree of specificity and sensitivity. At PND5, isoflurane had little effect on corticosterone levels in the blood, but increased corticosterone levels in the brain in a region-specific manner. At PND13, isoflurane increased corticosterone levels in the blood and brain, with a greater increase in blood than in brain. Taken together, these data indicate that during the SHRP, the brain increases local GC production in response to an acute stressor. These novel data indicate that the brain actively regulates local GC levels rather than simply being a passive recipient of systemic GCs produced by the adrenal glands.
P3.9 EXAMINING THE ROLE OF OXYTOCIN IN RESPONSE TO AVERSIVE VOCAL STIMULI FOLLOWING PAIR BOND FORMATION
Patrick Monari, Juliette Schefelker, Catherine Marler
Department of Psychology, University of Wisconsin USA
While the behavioral phenotype of an individual animal is generally considered to be fixed in social isolation, the social environment within which an animal exists can lead to alterations in behavioral responses. However, in monogamous vertebrates, little is known about how the formation of a pair bond modulates the behavioral phenotypes of the individuals within the pair bond. Recent evidence from our lab suggests that individuals of the monogamous bi-parental California mouse (Peromyscus californicus), displaying either proactive or reactive phenotypes, exhibit behavioral plasticity following pair bond formation; in an aversive vocal stimulus-approach task (VSAT), pair bonded individuals altered their behavior to become more similar to their mate. It is likely that social recognition and mate awareness are necessary to induce this behavioral change, however little is known about the biological mechanisms underlying behavioral plasticity following pair bonding. In the present study, we examined changes in approach behavior to an aversive conspecific vocal stimulus before and after pair bonding in conjunction with the administration of intranasal oxytocin (OT), a neuropeptide known to modulate several social behaviors, including individual discrimination and social bonding. We are also investigating the neural correlates of behavioral plasticity following the aversive VSAT and OT administration in pair bonded individuals by examining changes in immediate early gene (IEG) expression in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc), regions critical to social decision-making.
P3.10 TAMOXIFEN OR ESTRADIOL LIMITED TO THE INDUCTION PHASE ENHANCE THE EXPRESSION OF LOCOMOTOR SENSITIZATION TO NICOTINE 9 DAYS LATER IN OVARIECTOMIZED AND INTACT FEMALE RATS
Jennet L. Baumbach, Cheryl M. McCormick
Department of Psychology | Brock University Canada
Estradiol (E2) enhances nicotine-induced locomotor sensitization in rodents, but whether E2 is required during the induction phase and/or the expression phase is unknown. Here, ovariectomized (OVX) female rats were injected with 5µg estradiol benzoate (EB) 30 minutes before two nicotine (0.4mg/kg) administrations (induction phase), on challenge day (9 days later), at both time points, or at neither time point (4 groups, n=12/group). On each day that rats were given nicotine, locomotor activity (distance travelled) was quantified for 1hr after injection; sensitization was defined as the increase in distance travelled from induction to expression. Rats given EB during induction traveled further on expression day than on induction (p<0.001), while OIL pre-treated rats travelled equal distances during induction and expression (p=0.23). These results were replicated in Expt 2., where we administered 10µg of E2 instead of 5µg EB. Next, gonadally intact (Expt 3) or OVX (Expt 4) rats were administered the selective estrogen receptor modulator tamoxifen (1mg/kg) during the induction phase only. Tamoxifen enhanced expression of sensitization relative to OIL vehicle in both intact (p=0.021) and OVX (p <0.001) females. Although EB, E2 and tamoxifen all enhanced sensitization, EB and E2 are agonists of all forms of estrogen receptors, whereas tamoxifen is an antagonist of intracellular estrogen receptors [ERα/ERß] and an agonist of membrane bound g-coupled protein estrogen receptor 1 [GPER1]). Thus, E2 during induction enhanced expression of sensitization, even when absent at expression, which may involve actions at GPER1 (rather than ERα and ERß).
P3.11 MINERALOCORTICOID RECEPTORS ARE REQUIRED FOR THE DEVELOPMENT AND MAINTENANCE OF CA2’S MOLECULAR PROFILE AND FOR CA-2-DEPENDENT BEHAVIOR
Katharine E. McCann, Daniel J. Lustberg, Emma K. Shaughnessy, Kelly E. Carstens, Shannon Farris, Georgia M. Alexander, Serena M. Dudek
Neurobiology Laboratory | NIH/NIEHS USA
Exposure to stress is a risk factor in the development, onset, and exacerbation of several neuropsychiatric disorders, including depression, schizophrenia, and PTSD. Mineralocorticoid receptors (MRs) are critical for regulating behavioral responses to stress, and within the hippocampus, their highest expression is in area CA2. CA2 pyramidal neurons have a distinct molecular makeup resulting in a plasticity-resistant phenotype that distinguishes them from cells in CA1 and CA3. Thus, we asked whether MRs regulate CA2 neuron properties and related behaviors. Using three conditional knockout methods at different stages of development, we found a striking decrease in all tested CA2 markers, an effect mimicked by chronic antagonism of MRs. Furthermore, embryonic deletion of MRs also disrupted input into the hippocampus from the supramammillary nucleus and enabled synaptic potentiation of the normally LTP-resistant synaptic currents in CA2. We also found that CA2-targeted MR knockout was sufficient to disrupt behaviors observed with whole brain MR deletion. MR knockout mice exhibited normal social investigation behavior; however, these mice failed to discriminate between a familiar and a novel conspecific. In addition, MR knockout mice showed hyper-reactivity in response to novel objects. Finally, we tested the mice for anxiety-like behavior in an elevated plus maze and found that mice with a CA2-targeted deletion of MRs spent more time in the open arms of the maze, suggesting an anxiolytic-like behavioral phenotype. Together, these results demonstrate a novel role for MRs in regulating CA2’s molecular profile and provide insight into their role in regulating CA2-related behavior.
P3.12 TRKB ACTIVATION IS REQUIRED FOR 17β-ESTRADIOL-INDUCED ENHANCEMENT OF HIPPOCAMPAL MEMORY CONSOLIDATION
Kellie S. Gross, Randie Alf, Karyn M. Frick
Department of Psychology| University of Wisconsin-Milwaukee USA
The potent estrogen 17β-estradiol (E2) is known to enhance memory consolidation in object placement (OP) and object recognition (OR) tasks, however the molecular mechanisms underlying these effects are not fully understood. Brain derived neurotrophic factor (BDNF) is an important regulator of hippocampal memory and is also known to interact with E2, however whether BDNF plays a mechanistic role in E2-induced enhancement of memory consolidation remains unknown. Previously, we demonstrated that infusion of E2 into the dorsal hippocampus (DH) leads to increases in BDNF and pro-BDNF proteins via epigenetic modification of Bdnf gene promoters. Here, we examined the role that BDNF signaling with its receptor TrkB may play in the effects of E2 on hippocampal memory consolidation. To determine whether TrkB activity is required for the memory enhancing effects of E2, female C57BL/6 mice were ovariectomized and cannulated in the DH and dorsal third ventricle. Immediately following object training, mice were infused with vehicle or a non-memory impairing dose of ANA-12, a TrkB antagonist, into the DH and vehicle or E2 into the dorsal third ventricle. Object placement or object recognition memory was then tested 24 or 48 hours later, respectively. We found that ANA-12 blocked the memory-enhancing effects of E2, suggesting that BDNF/TrkB signaling is necessary for E2-induced memory enhancement. Current work is examining the molecular mechanisms that couple E2 to TrkB activation in the DH. In sum, this work will provide new insight into how E2 exerts its effects on hippocampal memory consolidation.
P3.13 HORMONAL RESPONSES TO BOTH REAL AND SIMULATED SOCIAL CHALLENGES IN A COMPETITIVE FEMALE BIRD
Elizabeth M. George, Alexandra B. Bentz, Sarah E. Wolf, Kimberly A. Rosvall
Department of Biology | Indiana University Bloomington USA
Many male vertebrates respond to aggressive encounters by elevating circulating testosterone (T) levels. Though there is growing evidence that female aggression is adaptive and that females can make and respond to T, we still lack a full understanding of how females hormonally respond to social challenges. We addressed this question in tree swallows (Tachycineta bicolor), a system in which females compete for limited nesting sites and female aggression is at least partially mediated by T. Here, we induced social challenges and measured T responses in pre-laying females in two ways: (1) using decoys to simulate territorial intrusions and (2) experimentally removing nesting sites to increase competition. We found that females did not elevate circulating T levels following real or simulated social challenges, despite showing aggressive responses, which stands in sharp contrast to our previous finding that females are physiologically capable of elevating T during this same breeding stage. Future work will investigate potential alternative mechanisms for responding to social challenges, such as socially modulating local (i.e., neural) T sensitivity instead of systemic T levels.
P3.14 GESTATIONAL EXPOSURE TO POLYCHLORINATED BIPHENYLS SHOW SEX AND BRAIN REGION SPECIFIC EFFECTS ON DOPAMINE MODULATING SYSTEMS IN ADOLESCENT RATS
Deborah Liberman, Katherine Walker, Hilvin Molina, Mariam Saleh, Haley Fuller, Alyssa Guzman, Margaret R. Bell
Department of Biological Sciences and Health Sciences | DePaul University USA
Polychlorinated biphenyls (PCBs) are environmental contaminants known to be acutely neurotoxic, immunotoxic, and endocrine-disrupting. However, little is known about how PCBs affect hormone-sensitive immune signaling in the brain. Exposure to PCBs is highest during gestation and infancy, periods crucial to neurodevelopment and sensitive to hormones and therefore perturbation. Development of dopaminergic systems linked to reproductive and behavioral maturity continue to occur through adolescence. Dopaminergic signaling is sensitive to disruption by both PCBs and neuroinflammation. Therefore, this study tests the hypothesis that perinatal PCB exposure with or without later inflammatory challenge alters expression of dopaminergic genes in hypothalamic and mesocorticolimbic systems in adolescence. To do so, Sprague-Dawley rats were exposed to an environmentally relevant mixture and dose of PCBs (or vehicle) perinatally and adolescent offspring were given lipopolysaccharide (LPS, or vehicle) 3-4 hours prior to brain tissue collection. Exposure to PCBs increased expression of both Drd1a and Drd2 dopamine receptors only in males in the hypothalamus but not midbrain, prefrontal cortex, or striatum. Given the greater hormone sensitivity of the hypothalamus relative to the other brain regions studied, and the sex-specific effects, these results indicate endocrine mechanisms of PCB action. These adolescent results differ from those found in neonatal animals, where dopaminergic enzymes and transporters but not receptors were altered by PCBs. It is possible that neonatal changes in outcomes related to dopamine content later drive adolescent changes in dopamine sensitivity. This highlights the importance of studying endocrine disrupting compounds in both sexes and in developmental contexts.
P3.15 DEVELOPMENTAL EFFECTS OF POLYCHLORINATED BIPHENYLS (PCBS) ON ACTIVATIONAL MORPHOLOGY OF MICROGLIA IN THE ADULT BRAIN
Katherine Walker, Simone Rhodes, Margaret R. Bell
Departments of Biological Sciences, and Health Sciences | DePaul University USA
Polychlorinated biphenyls (PCBs) are environmental contaminants known to cause sex-specific changes in hormone signaling in the brain as well as perturbations in peripheral immune function. The possible effects on microglia, an immune cell in the brain, however, are not known. This study tests the hypothesis that developmental exposure to PCBs has sex-specific effects on microglia in the adult prefrontal cortex, either on basal number or activational status, or microglial responses to an immune challenge by lipopolysaccharide (LPS). Pregnant Sprague-Dawley rats were given an environmentally relevant mixture and dose of PCBs or oil orally during gestation. Adult offspring were given an injection of LPS or saline 24 hours prior to euthanasia. Immunohistochemistry was performed to label microglia with IBA1 and then quantify activational status. Microglia tend to exist in a ramified state under basal conditions, and become hyperramified and then reactive upon detecting inflammatory signals. Preliminary data indicate that males are more sensitive to the low doses of LPS used in this experiment, as males exposed to LPS showed more hyperramified microglia than saline exposed animals. However, effects of PCBs and interactions between PCB and LPS on the number of ramified and reactive microglia was found in females but not males. Analysis of tissue co-labeled for IBA1 and TLR4 is ongoing. These results indicate that developmental PCBs can alter microglial activity in the adult brain; this is of great interest given the role of microglia and neuroimmune functions in a host of neural disorders.
P3.16 MELATONIN FACILITATES SEASONAL CHANGES IN STEROIDOGENESIS AND AGGRESSIVE BEHAVIOR IN MALE SIBERIAN HAMSTERS
Kathleen M. Munley, Jessica E. Deyoe, Catherine H. Adaniya, Andrea M. Nowakowski, Clarissa C. Ren, Grace V. Murphy, John M. Reinhart, Gregory E. Demas
Department of Biology and Center for the Integrative Study of Animal Behavior | Indiana University USA
Numerous studies across animal taxa have demonstrated a positive correlation between gonadal steroids and aggression during the breeding season. However, it is becoming increasingly clear that alternative neuroendocrine mechanisms, which are independent of circulating gonadal steroids, are critical in modulating aggressive behavior. Such mechanisms are particularly important for seasonally-breeding animals that are more aggressive during the short-day (SD) photoperiods of the non-breeding season, despite gonadal regression and reduced circulating steroid levels. While the mechanisms underlying SD aggression are not well understood, previous work from our lab suggests that the pineal hormone melatonin and the adrenal androgen dehydroepiandrosterone (DHEA) are important in facilitating non-breeding aggression in Siberian hamsters (Phodopus sungorus). To investigate the role of melatonin in mediating seasonal changes in steroid synthesis and aggressive behavior, we housed male hamsters in long days (LD) or SD, treated them with either timed melatonin or saline injections, and quantified aggression after 9 weeks of photoperiodic housing. Following behavioral testing, we assessed whether melatonin mediates seasonal changes in steroidogenesis by measuring circulating hormone levels and neurosteroid levels in regions of the social behavior network that are associated with aggressive or reproductive behaviors. LD hamsters administered melatonin (LD-M) exhibited SD-like levels of aggression. Interestingly, LD-M and SD animals reduced circulating DHEA and T in response to an aggressive encounter, whereas LD animals elevated circulating androgens. Neurosteroid profiles will also be presented and compared across brain regions and seasonal phenotypes. Collectively, this study provides insight into how melatonin modulates the neuroendocrine circuits underlying seasonal aggression.
P3.17 ROLE OF VASOPRESSIN IN THE VENTRAL PALLIDUM IN REGULATING JUVENILE SOCIAL PLAY BEHAVIOR
Jessica D.A. Lee, Remco Bredewold, Alexa H. Veenema
Psychology | Michigan State University USA
Social play is predominantly displayed by juveniles of many mammalian species, including rodents and humans. Engagement in social play helps develop social competence throughout life. Children diagnosed with autism spectrum (ASD) show decrease involvement in social play. Moreover, ASD is more prevalent in males than females. Thus, there is a need to better understand the neural mechanisms underlying social play in both sexes. We recently showed that vasopressin acting in the lateral septum (LS) of juvenile rats regulates social play behavior in a sex-specific manner. Vasopressin projections to the LS originate in the bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA). We further showed that the ventral pallidum (VP) also receives vasopressin projections from these two regions. Here, we hypothesized that, similar to the LS, vasopressin in the VP regulates social play in a sex-specific manner. We found that the VP and LS show a similar sex difference in vasopressin fiber density, with denser vasopressin fibers in juvenile males. In contrast, VP and LS show a brain region-specific sex difference in vasopressin 1a receptor (V1aR) binding density, with denser V1aR binding in the female LS and male VP. Using a specific V1aR antagonist, we are currently determining the effects of V1aR blockade in the VP on social play behavior in juvenile males and females. This study will provide insights into the brain regions recruited by vasopressin for the regulation of social play behavior as well as the larger neural network modulated by the BNST/MeA-vasopressin system.
P3.18 EFFECTS OF SOCIAL INSTABILITY STRESS IN ADOLESCENCE IN FEMALE RATS ON SOCIAL INTERACTION AND GENE EXPRESSION IN SOCIAL BRAIN REGIONS
Pardis Asgari, Travis E. Hodges, Jennet L. Baumbach, Cheryl M. McCormick
Departments of Biological Sciences and Psychology | Brock University Canada
Adolescence is an important time of development of social brain regions. Social instability stress in adolescence (SS; daily 1h isolation+change of cage partner postnatal days [P] 30-45) leads to deficits in social behavior in SS rats compared with controls (CTL) in males; less is known in females. In expt1, SS and CTL male and female rats underwent a social interaction (SI) test soon (P46) or long (P70) after the SS. Irrespective of time post-stress and sex, SS rats spent less time in SI than CTL rats (p=0.002), although females spent less time in SI than males (p<0.001). Thus, these results replicated our previous findings of decreased SI after SS in males and extend them to females. In expt2, the effect on SI in females was not replicated (smaller sample). Nevertheless, SS females had higher corticosterone concentrations and lower Zif268 immunoreactive cell counts in the cingulate and infralimbic cortices after SI than did CTLs at P46 (all p<0.01) and did not differ from CTLs at P70. In expt3, brains were collected at P46 and P70 for RT-qPCR. Effects of SS on expression were observed for glucocorticoid receptor, mineralocorticoid receptor, and oxytocin receptor that depended on age and brain region (prefrontal cortex, hippocampus). There was effect of SS for corticotrophin releasing hormone receptor or vasopressin receptor1 at either age. These results extend our findings of long-lasting heightened responses to psychostimulants and decreased spatial memory after SS in females to show that their social development also is altered.
P3.19 NEUROPROTECTION OF SPHINCTER MOTONEURONS WITH GONADAL HORMONES AFTER SPINAL CORD INJURY
Dale R. Sengelaub, Xiao-Ming Xu
Psychological and Brain Sciences | Indiana University
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery, Indiana University School of Medicine USA
Spinal cord injury (SCI) results in lesions that destroy tissue and spinal tracts, leading to deficits in locomotor function. We have shown that after SCI, surviving somatic motoneurons undergo dendritic atrophy that can be prevented by treatment with gonadal hormones. SCI also results in deficits in autonomic function, with urinary problems being the most common reported by SCI patients. Here we tested if treatment with estradiol (E) and dihydrotestosterone (DHT) has similar protective effects on sphincter motoneuron structure and function after SCI. Gonadally intact young male rats received either a sham or a T9 contusion injury. Immediately following contusion, rats were implanted with subcutaneous Silastic capsules filled with E and DHT or left blank. Urinary void frequency and volume were measured at 3 weeks after SCI. One week later, motoneurons innervating the external urethral sphincter (EUS) muscle were labeled with cholera toxin-conjugated HRP, and dendritic arbors were reconstructed in three dimensions; lesion volume, and tissue sparing were also assessed. Void frequency decreased and void volume increased after SCI; both were dramatically improved by treatment with E+DHT. Contusion injury resulted in large spinal cord lesions, and treatment with E+DHT had no effect on lesion size or spared white and gray matter. Similar to what we have previously reported for somatic motoneurons, dendritic length in EUS motoneuron was decreased by 42% after SCI, and this atrophy was prevented by treatment with E+DHT. Together, these results indicate that the use of gonadal hormones could be an effective treatment after SCI.
P3.20 TUMOR-INDUCED COGNITIVE DYSFUNCTION: A ROLE FOR ESTROGENS?
Kathryn L.G. Russart 1,2, Lindsay Strehle 1, Valerie Burch1, Alena Oates1, Ann Thomas1, Ashley Lahoud1, Jasskiran Kaur1, Cole McGinnis1, Leah Pyter1,2,3,4
1Institute for Behavioral Medicine Research, 2Comprehensive Cancer Center, 3Department of Psychiatry, 4Department of Neuroscience | The Ohio State University USA
Breast cancer patients frequently experience cognitive dysfunction during and after treatment. Recent studies indicate the cause of cognitive impairment is likely multi-modal; chemotherapy, tumor biology, surgery, stress, and hormones are all potential contributors. The majority of breast cancer patients are post-menopausal, and therefore have low levels of circulating estrogens. Additionally, many survivors are treated with long-term (>20 years) estrogen receptor antagonists or aromatase inhibitors. Therefore estrogens, which are involved in modulation of cognition, might be involved in cancer-related cognitive impairment. We investigated the effects of a breast cancer tumor and its removal on cognitive performance and serum estradiol-17β (E2) in a mouse model of breast cancer. Intact and ovariectomized (OVX) mice were given tumors (or sham surgery), and half of the tumors were subsequently resected (survivors). OVX mice performed more poorly than intact mice during cognitive tasks such as the novel object recognition and fear conditioning tests, and the presence of a tumor reduced performance further. Uteri weighed less and serum E2 concentrations were reduced with ovariectomy, but E2 was modulated by tumor and tumor resection. Intact mice with tumors had disrupted estrous cycles; they spent more days in diestrus (and fewer days in metestrus), and some tumor-bearing mice discontinued cycling. Lastly, hippocampal expression of estrogen receptor α, pro-inflammatory Il-1β and Il-6, and syanaptogenesis genes Syn and Bdnf was modulated with tumors and tumor resection. Thus, neural inflammation and synaptic plasticity, both estrogen-mediated events, are potential contributors to the observed cognitive dysfunction.
P3.21 DO CAVITY-NESTING SPECIES HAVE REDUCED SEXUAL DIMORPHISM IN GENE EXPRESSION AND HORMONAL VARIATION?
Sara E. Lipshutz, Kimberly A. Rosvall
Department of Biology | Indiana University USA
In many animals, aggression is critical for competition over nest sites, and can determine which individuals get to reproduce. This is particularly true for cavity-nesting birds that must locate cavities to nest. In cavity-nesting species, both males and females compete to acquire and defend nesting territories in addition to males. Female aggression has only recently been recognized as an adaptive behavior and how its underlying genomic and hormonal mechanisms compare to those of males is not well understood. We compare circulating testosterone (T) along with neural gene regulation of sex steroid receptors influencing aggression between male and female cavity- and non-cavity-nesters, to understand how both gene expression, and hormonal modulation of the behaviors they regulate, might contribute to functional adaptations of the cavity-nesting phenotype. If selection acts similarly on the sexes within cavity-nesters but not their close relatives, we might expect reduced sexual dimorphism in hormonal and gene expression profiles across cavity-nesters. This hypothesis is supported in a pair of species (family Turdidae) during territorial establishment: testosterone (T) levels in cavity-nesting Sialia sialis females were significantly higher compared to non-cavity-nesting Turdus migratorius females, but males did not differ in T levels. These results are consistent with the hypothesis that convergent selection on male and female cavity-nesters to compete over territories could minimize sex differences in underlying mechanisms, via ‘masculinization’ of females.
P3.22 SEASONAL SHIFTS IN NEURAL GENE EXPRESSION IN A TERRITORIAL FEMALE SONGBIRD
Alexandra Bentz, Douglas Rusch, Kimberly Rosvall
Department of Biology | Indiana University USA
Aggressive behaviors typically decline seasonally as animals transition from a period of intense social instability to parental care, and decades of research in males suggests declining testosterone (T) levels mediate this seasonal pattern. However, in females, which can face reproductive consequences of elevated T even prior to the arrival of offspring, it is still unclear how aggression is regulated. An emerging model organism for female-female competition is the tree swallow (Tachycineta bicolor), the females of which fiercely compete for territories early in the breeding season. Aggression in these females is, in part, T-mediated; however, females demonstrate the ability to display aggression past the seasonal decline in T that occurs during incubation. Here, we use RNA-seq to explore seasonal patterns of gene expression across three behaviorally relevant neural tissues (hindbrain, nucleus taenia, and hypothalamus) and test the hypothesis that aggression-related genes show differential expression from territory establishment to incubation. We found hundreds of differentially expressed genes in the nucleus taenia and hypothalamus, while expression in the hindbrain remained relatively stable. Gene Ontology analyses revealed that processes related to neural plasticity changed across breeding stages, along with processes related to activity, self-maintenance, and immune function. We also found a potential shift in the neurogenomic mechanisms regulating aggression, with genes related to sex steroids being upregulated during territory establishment and non-steroidal genes (e.g., nonapeptides) being upregulated during incubation. Collectively, these data highlight important gene regulatory pathways that may underlie behavioral plasticity in females.
P3.23 METHOD MATTERS; CONSIDERATIONS FOR REPORTING HPA NEGATIVE FEEDBACK
Christine R. Lattin, Tosha R. Kelly
Department of Biological Sciences | Louisiana State University USA
Because of the importance in being able to shut down the glucocorticoid response once a stressor is over, many researchers have become increasingly interested in assessing the hypothalamic-pituitary-adrenal (HPA) negative feedback system. However, there are several defensible ways to report negative feedback efficacy, each of which incorporates various aspects of HPA physiology. Here, we review six different methods for reporting HPA negative feedback and their prevalence in the literature, and reanalyze a dataset of wild house sparrows (Passer domesticus; n=58) caught during different life history stages to show that even though most of the methods give values that are correlated with each other, they yield distinct statistical results. Because the method of reporting negative feedback matters so much for the end results, we encourage researchers to converge on a common method for reporting HPA negative feedback, or at the very least, make raw data available so alternative measures can be calculated. We also advise caution in comparing results among studies using different methods to assess HPA negative feedback.
P3.24 RE-EVALUATING TESTOSTERONE AS A PHENOTYPIC INTEGRATOR
Kimberly A. Rosvall and Sarah E. Lipshutz
Department of Biology | Indiana University USA
Testosterone (T) co-regulates many different fitness-related traits, generating an integrated set of phenotypes that work well together, e.g. courtship displays, aggression, and enhanced spermatogenesis during social competition. Thus, T is thought to play a central role in behavioral evolution; however, its structure and function are highly conserved over millions of years of evolution. This apparent paradox may be resolved if the evolution of T-mediated traits is achieved via independent regulation of one or more components of endocrine systems. Here, we evaluate regulation and evolution of these integrated phenotypes, focusing on T, its cognate receptor (androgen receptor) and related endocrine components. We pose predictions about the endocrine mechanisms generating organismal phenotypic integration, and we assess these predictions using data that we have generated from wild birds over the last decade. We find limited support for integration across developmental and evolutionary time, and we close by highlighting research priorities that will enhance our understanding of behavioral evolution by continued cross-talk between behavioral ecology and endocrinology.
P3.25 KNDy NEURONAL SENSITIVITY TO GHRELIN AND THE IMPACT OF 17 BETA-ESTRADIOL
Kristie Conde1,2, Allison Vanschaik2, Yuxiang Sun3, and Troy A. Roepke2
1Department of Neuroscience and Cell Biology, Rutgers School of Graduate Studies, 2Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers University USA, 3Department of Nutrition and Food Science, Texas A&M University, College Station USA
The gut peptide, ghrelin, potentially mediates negative energy states and the neuroendocrine control of reproduction by acting through its receptor, growth hormone secretagogue receptor (GHSR). GHSR is expressed in hypothalamic arcuate (ARC) Kisspeptin/Neurokinin B/Dynorphin (KNDy) neurons, known to regulate reproduction and energy balance. We have previously shown 17-beta-estradiol (E2) increases Ghsr expression in KNDy neurons 6-fold, increasing their sensitivity to ghrelin. We hypothesize that E2-induced GHSR expression augments KNDy sensitivity during states of elevated ghrelin (fasting) to disrupt reproduction and reduce energy expenditure in females. We developed a Kiss1-specific GHSR knockout to determine the impact of GHSR in ARC KNDy neurons. We found no differences in vaginal opening or estrous cyclicity between experimental and control females. In ovariectomized females with or without E2 replacement, metabolic rates (V.O2, V.CO2) and substrate utilization (RER) were lower in experimentals and food intake and activity were increased in E2-treated experimentals compared to controls. Fasting glucose levels were higher in experimentals than in controls, regardless of steroid. In a separate cohort of mice, Luteinizing Hormone (LH) pulsatility was measured in fasted and ghrelin injected experimentals and controls. Fasting reduced LH pulses in control females, but not experimental females and ghrelin reduced LH in OVX+E2 control females about 90 min post-injection but not in 2 of 3 OVX+E2 experimentals. Collectively, these data suggest that GHSR activation in KNDy neurons modulates metabolism, glucose homeostasis, and LH pulsatility and illustrates a novel mechanism for E2 and ghrelin to control KNDy neurons and their physiological functions.
P3.26 THE ROLE OF SOCIAL REWARD IN RELATION TO PAIR BOND FORMATION AND MAINTENANCE IN ZEBRA FINCHES
Nora H Prior, Chelsea M. Haakenson, Gregory F. Ball
Department of Psychology | University of Maryland College Park USA
Socially monogamous partnerships involve many behavioral components that vary both within and across species. Zebra finches are relatively unique as a small songbird that maintains strong life-long partnerships. Here we used a conditioned place preference (CPP) paradigm to compare the reinforcing properties of a mate during courtship and pair maintenance. Briefly, our CPP paradigm had three stages. (1) Pre-Test: each partner was exposed to the full cage. (2) Reward-Conditioning: each pair was housed on half of the cage (either a yellow or blue side). (3) Post-Test: each partner again had access to the full cage. Time spent on the conditioned side was compared during the Pre-Test and Post-Test. The zebra finches only formed CPP during courtship, and this effect was much stronger in females. The strength of the CPP during courtship was not strongly related to whether or not the pair copulated during the conditioning phase. This experiment suggests that while social reward is clearly important for courtship, it is possible that it plays less of a role in pair-bond maintenance. Such an effect could be consistent with the effect of pair bonding on the dopamine system described in mammals. To further compare the role of social reward during pair bonding, we are currently conducting two follow-up experiments. Firstly, we are quantifying the effect of D1 and D2 agonists on CPP during courtship and pair maintenance, and secondly, we are describing changes in the reinforcing value of the partner during the early weeks of pair bonding.
P3.27 EDC MIXTURE DISRUPTS MATERNAL BEHAVIOR AND THE HYPOTHALAMIC CONTROL OF PUBERTY TRANSGENERATIONALLY THORUGH EPIGENETIC MECHANISMS
López-Rodríguez, David¹; Aylwin, Carlos Francisco⁴; Gérard, Arlette¹; Blacher, Silvia²; Tirelli, Ezio³; Noël, Agnès²; Bourguignon, Jean-Pierre¹; Lomniczi, Alejandro⁴; Parent, Anne-Simone¹
¹GIGA Neurosciences, Neuroendocrinology Unit, ²Tumor and Development Biology, GIGA-Cancer, ³Department of Psychology: Cognition and Behavior, University of Liège, Belgium, ⁴Division of Genetics, Oregon National Primate Research Center USA
Endocrine disrupting chemicals (EDCs) are a rising concern for public health due to their ubiquity as complex mixtures. Our goal was to study the effect of an EDC mixture on female sexual development during 3 generations.
Female rats (F0 generation) were orally exposed to a mixture of 13 anti-androgenic and estrogenic EDCs or corn oil for 2 weeks before gestation until weaning. The mixture was composed of plasticizers, fungicides/pesticides, UV filters, parabens and acetaminophen at doses representing human exposure. Sexual development (vaginal opening, GnRH secretion, estrous cyclicity and folliculogenesis) and maternal behavior were studied from F0 to F3 generations. At PND21, mediobasal hypothalamus of the F1 and F3 were removed for gene expression, histone modifications and DNA methylation analysis of target genes.
F1 and F2 females showed decreased maternal licking behavior while spending more time resting alone. F2 and F3 females showed delayed vaginal opening, decreased percentage of regular estrous cycle, decreased GnRH interpulse interval and altered late stage folliculogenesis. This phenotype was associated with transcriptional and epigenetic alterations of hypothalamic genes involved in reproductive competence and behavior like kisspeptin (Kiss1), oxytocin (Oxt), estrogen (Esr1), glutamate (Grin2d), dopamine signaling (Th) as well as glucocorticoid activity (Nr3c1 and Crh). We have found alterations in repressive (H3K27me3, H3K9me3) or active (H3K4me3, H3K9ac) histone marks concomitant with transcriptional activity.
Overall, gestational and lactational exposure to an environmentally relevant EDC mixture transgenerationally affects sexual development throughout epigenetic reprogramming of the hypothalamus. Some of the effects could be mediated by alterations of maternal behavior.
P3.28 EFFECTS OF EARLY-LIFE EXPOSURE TO CLOMIPRAMINE ON SOCIOEMOTIONAL BEHAVIORS AND INFLAMMATION
Christina M. Ragan, Brea Regula, Lindsay M. Gielda
Psychology | Purdue University Northwest USA
Dramatic hormonal fluctuations that occur during the peripartum period can lead to alterations in brain chemistry that result in postpartum mood and anxiety disorders. Recent research has highlighted the role of the immune response in the pathogenesis of these mood and anxiety disorders in non-maternal populations. In fact, in non-maternal populations, inflammation in brain regions such as the orbitofrontal cortex (OFC) is 30% higher in people with obsessive-compulsive disorder (OCD) compared to healthy controls. Less is known about inflammation in the brain of postpartum females. Using a pharmacologically-induced model of OCD in Sprague-Dawley rats, we exposed pups to the tricyclic antidepressant, clomipramine, during postnatal days 9-16 or a saline control. We observed that during the postpartum period, rat mothers previously-exposed to clomipramine during early development engaged in more passive nursing postures and more OCD-like behavior compared to control mothers. The rat mothers that experienced early exposure to clomipramine also expressed more pro-inflammatory IL-1β in the OFC compared to saline control mothers. We are currently analyzing additional pro- and anti-inflammatory markers in these mothers and in males. Our findings suggested that increased inflammation in the OFC may be a mechanism associated with OCD behavior in maternal and non-maternal populations.
P3.29 AAS INCREASE SENSITIVITY TO DOPAMINE D2 RECEPTORS FOR RATS IN AN EFFORT DISCOUNTING TASK
Alexandra M. Donovan, Malin Kallstrom, Ruth I. Wood
Neuroscience Graduate Program | University of Southern California, Uppsala University Sweden
Anabolic androgenic steroids (AAS) are performance-enhancing drugs used by world-class and rank-and-file athletes. AAS abuse is linked with risky decision-making, ranging from drunk driving to unsafe sex. Our lab uses operant behavior in rats to test effects of AAS on decision making. In our previous study, AAS rats worked harder for a food reward. In an operant discounting task, rats chose between a small easy reward (1 lever press for 1 sugar pellet) and a large difficult reward (2, 5, 10, or 15 presses for 3 pellets). Rats treated chronically with testosterone (7.5mg/kg) previously showed a greater preference for the large reward lever vs controls. Effort discounting is sensitive to dopamine, and AAS alter dopamine receptor expression in reward circuits. We determined if AAS increase sensitivity to dopamine D1 antagonist (SCH23390) or D2 antagonist (eticlopride) during effort discounting. There was no effect of AAS on effort discounting at baseline (large reward selection at FR5: AAS-treated rats 69.0±5.0%, vehicle-treated rats 74.5±4.4%). At 0.01mg/kg, the D1 antagonist significantly reduced large reward preference across both groups (FR5: AAS: 33.3±10.1%, vehicle: 42.1±9.6%, F(1,16)=24.1). In response to D2 antagonist eticlopride(0.06mg/kg) there was an effect of testosterone (F(1,16)=7.8), an effect of eticlopride (F(1,16)=50.5), and an eticlopride x testosterone interaction (F(1,16)=9.9) with greater reduction in AAS-treated rats (FR5: AAS: 30.2±7.2%, vehicle: 48.1±9.2%). This suggests that AAS alter effort-based decision making via increased sensitivity to dopamine D2 receptors.
P3.30 NEONATAL PROGESTERONE IMPAIRS COGNITIVE FUNCTION
Rebecka O. Serpa1, Christine K. Wagner2, Ruth I. Wood1
1Integrative Anatomical Sciences | Keck School of Medicine of USC USA, 2University of Albany USA
The synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC) is routinely used for the prevention of premature birth in at-risk women, despite little understanding of potential effects on developing brain. Our work in rodents suggests that the developing brain is sensitive to progestins. Previous studies have shown that 17-OHPC impairs performance in set-shifting and delay discounting tasks. In the current study, we investigated the effects of 17-OHPC (0.5mg/kg) or vehicle from postnatal days 1 through 14 on cognitive function in adulthood. Cognitive function was assessed in males and females (n=8-10/group) by operant responding for sugar pellets, measuring delayed reinforcement or reversal learning. For delayed reinforcement, the rat must wait 15 seconds for pellets after responding on a lever. Delay is signaled by a light or unsignaled. For reversal learning, the rat must respond on the lever under a stimulus light, and then learn to respond on the unlit lever. For delayed reinforcement, rats earned more pellets under signaled vs unsignaled conditions. Likewise, males made more responses and earned more pellets, compared with females. 17-OHPC-treated rats earned fewer pellets than controls when a light was present. For reversal learning, results were similar. With rule reversal, females required more trials than males, and 17-OHPC-treated rats required more trials than controls. This suggests that 17-OHPC during development may alter cognitive function. These developmental neurobehavioral effects of a drug in widespread clinical use during pregnancy highlight the need to re-evaluate benefits and potential outcomes of a prophylactic progestin administration for the prevention of premature delivery.
P3.31 ACUTE SOCIAL DEFEAT STRESS DRIVES NEUROINFLAMMATION VIA MICROGLIAL PRIMING IN THE vmPFC
Alex Grizzell, Thomas T. Clarity, Matthew A. Cooper
Department of Psychology and Neuroscience and Behavior | University of Tennessee USA
With growing interest in the intersection between psychological stress and the immune system, there is little doubt that the two are heavily intertwined, especially in prolonged stress conditions. Nevertheless, we know little regarding whether acute psychological stress drives an innate immune response. The ventromedial aspect of the prefrontal cortex (vmPFC) is critical for emotion regulation during acute stress and has been argued to mediate stress resiliency. On the other hand, this region is especially vulnerable to highly salient stress experiences, such as those occurring during acute social defeat stress. Indeed, we have shown susceptibility to such stress corresponds with increased risk for oxidative stress in the vmPFC. In this study, we demonstrate that an acute social defeat stressor drives a marginal recruitment of vmPFC microglia, the resident immune cells of the brain. Importantly, the degree of microglial activity is greatly increased if the subject is given a subsequent immune challenge via an intraperitoneal injection of the endotoxin, lipopolysaccharide (LPS). Male Syrian hamsters were acutely defeated and, 24 hours later, injected with 0, 20, 100, or 500 ug/kg LPS. All animals were then euthanized 4 hours after defeat. Immunolabeling for the proteins Iba-1 and CD68 were then performed on vmPFC tissue, to determine microglial morphology and likelihood of phagocytosis, respectively. We found a LPS dose-dependent increase in the microglial response which was exaggerated by acute social defeat stress. This indicates that even an acute social stress can drive neuroinflammatory processes which, if unchecked, could prove detrimental to vmPFC anatomical integrity.
P3.32 PACED MATING BEHAVIOR IN SEXUALLY EXPERIENCED RATS IS INFLUENCED BY LATENCY TO RECEIPT OF EJACULATIONS AND HORMONE REGIMEN
Sarah H. Meerts, Sophie L. Bokor, Helen Paglia, Yoojin Kim
Department of Psychology | Carleton College USA
Paced mating behavior varies both as a function of sexual experience and the criterion used to end the test. Sexually experienced female rats spend more time with the male, return faster after intromissions, and display more proceptive behaviors near the male relative to sexually naïve rats. Additionally, experienced rats take significantly longer to return after ejaculation than naïve rats when the test end criterion is 30 minutes but not 15 intromissions. Experiment 1 explored whether the difference in contact-return to ejaculation is better explained by learning across tests or latency to receive each ejaculation when mating. Return latency to the first three ejaculations in each of four mating tests, ending at 30 minutes or 15 intromissions, was assessed. Rats receiving 30-minute tests showed significantly longer return latencies after the second and third, but not first, ejaculations than rats receiving 15 intromission tests. Experiment 2 tested whether hormone regimen affects paced mating behavior in sexually experienced rats. Sexually experienced rats were primed with 10 ug estradiol benzoate (EB) + 1 mg progesterone (P) or EB-Alone (2 ug EB for 6 days) and received a 15-intromission paced mating test. Rats primed with EB-Alone were fully receptive, but showed significantly longer latency to return after intromissions and ejaculations, significantly less time with the male, and significantly longer test durations compared to being primed with EB+P. Future experiments are needed to determine physiological processes factoring into heightened sensitivity to stimulation with longer latencies to multiple ejaculations or when tested with EB-Alone.
P3.33 INVESTIGATING CELLULAR MECHANISMS OF COPING RESPONSES AND DOMINANCE STATUS
Megan K. Cannon, Emily L. Graham, Max D. Burzinski, Neha Sagarad,Matthew A. Cooper
Department of Psychology | University of Tennessee USA
There are a great deal of individual differences in how humans and other animals cope with stress. Differences in coping are linked to several environmental factors, including social dominance. This study investigated whether coping responses predict dominance status in male and female Syrian hamsters and whether the maintenance of dominance relationships alters subsequent coping responses. The study also investigated underlying cellular mechanisms by dual immunofluorescence labelling for deltafosB and dopamine type-1 receptors within the nucleus accumbens. We hypothesized that the maintenance of dominance relationships would increase active coping strategies in dominants and passive coping strategies in subordinates. Finally, we hypothesized that animals with a proactive response will express higher levels of deltafosB and dopamine type-1 receptors in the nucleus accumbens. Male and female hamsters were paired with a same-sex partner in daily aggressive encounters for two weeks. To assay coping strategies before and after the formation of dominance relationships, we tested animals in a series of behavioral tests, including open field, novel object exploration, elevated zero maze, light/dark transition, Porsolt forced swim, and social defeat tests. We found that dominance status has a greater effect on stress-induced anxiety-like and depression-like behavior in male hamsters compared to female hamsters. Because most preclinical neuroscience research is conducted exclusively in male animals, these data will extend our understanding of sex-differences in the expression of passive and active coping strategies. In addition, these data indicate that dominance status plays a role in the development of coping strategies and stress vulnerability.
P3.34 CASTE BUT NOT SEX DIFFERENCES IN THE EFFECTS OF SOCIAL NOVELTY ON CELL PROLIFERATION IN A EUSOCIAL MAMMAL
Troy Collins, Mariela Faykoo-Martinez, Matthew Kolisnyk, Heidi Cheng, Melissa Holmes
Psychology | University of Toronto Mississauga Canada
Changes in the social environment can influence adult neurogenesis in a manipulation- and sex-dependent manner. For example, male hamsters exposed to novel aggressive individuals show increased olfactory bulb neurogenesis. Group-housed rats given chronic electric shocks do not have sex differences in new neuron survival. However, socially isolated males display decreased new neuron survival while females display an increase following shock. Naked mole-rats (NMR) are eusocial mammals with large colony sizes dominated by a single breeding female. Subordinate NMRs have increased doublecortin expression in the basolateral amygdala when paired with a novel female, but not a novel male, suggesting a sex-specific increase in threat assessment. Furthermore, female same-sex pairs display less huddling and more shoving than male same-sex pairs, consistent with their competitive matriarchal hierarchy. We examined the effects of exposure to a novel or familiar NMR on cell proliferation in neurogenic brain regions. We injected EdU, a marker of cell division, into sex-balanced groups of adult subordinate soldier and worker NMRs and paired them for 30 minutes with either a familiar or novel conspecific every 24 hours for 7 days. We then quantified EdU expressing cells in the dentate gyrus (DG), subventricular zone (SVZ), and olfactory bulb. We show that soldiers have higher levels of SVZ cell proliferation than workers. Exposure to novel animals decreased cell proliferation in the DG. Our findings suggest a caste differentiated response to unfamiliar individuals. Soldiers may be more primed to detect odor cues, reflected by a caste-specific difference in proliferation in the SVZ.
P3.35 DECIPHERING EXPERIENCE-DEPENDENT PLASTICITY IN MATERNAL PUP GATHERING BEHAVIOR USING ADULT FEMALE RETT SYNDROME MICE
Dana E. Layo, Billy Y.B. Lau, Anu Kumar, Keerthi Krishnan
Biochemistry & Cellular and Molecular Biology | University of Tennessee, Knoxville USA
Cohabitation of adult nulliparous mice with pups and mother induces maternal behavior in them in a hormone-independent manner. Such non-hormonal factors are thought to be important in mediating plasticity, likely through chromatin remodeling of specific neural circuitry (Stolzenberg and Champagne, 2016). We have previously shown that nulliparous mice deficient in Methyl CpG-binding protein 2 (MECP2) display inefficient pup gathering behavior, likely due to atypical auditory processing of ultrasonic vocalizations from pups (Krishnan, Lau et al, 2017). Furthermore, we identified a crucial mechanism involving extracellular matrix structures called perineuronal nets (PNNs) which play a major role in structural plasticity of parvalbumin+ GABAergic networks in the auditory cortex. The auditory cortex of MECP2-deficient females had increased numbers of PNNs, which when removed, improved pup gathering performance, demonstrating the crucial structural role that PNNs provide in learning and plasticity.
Many questions remain: How do the nulliparous wild types learn and perform the behavior well? What neural circuits are critical for this learning? By using whole brain immunostaining, imaging and quantification approaches, we found that regions in the primary somatosensory cortex of adult wild type female undergo dynamic changes in PNN expression after learned maternal behavior experience. Mecp2-deficient females exhibit atypical PNN expression before and after this experience, which is correlated with their inefficient pup retrieval performance. Taken together, our data suggest that MECP2 regulates the expression of PNNs, in a region-specific, hemisphere-specific manner, thereby affecting adult plasticity essential for learning and execution of efficient pup retrieval task.
P3.36 THE INFLUENCE OF DIETARY CHOLINE ON HIPPOCAMPAL α7 NICOTINIC ACETYLCHOLINE RECEPTORS
Colin Maxie, Catherine Adams, Jennifer Garner, Kalynn Schulz
Department of Psychology | University of Tennessee, Knoxville USA
Prenatal stress is associated with deficits in learning and memory. These changes may be due, at least in part, to alterations in α7 nicotinic acetylcholine receptors (nAChRs). nAChRs are well-known mediators of learning and memory, and prenatal stress changes levels of these receptors in the hippocampus and prefrontal cortex. Our lab has found that intake of dietary choline during gestation rescues the negative effects of prenatal stress on adult spatial memory function. However, the mechanisms by which choline mitigates the negative effects of prenatal stress on memory function are unknown. Choline is a direct agonist of α7 nAChRs. Therefore, we hypothesize that choline mitigates the effects of prenatal stress on memory function via changes in hippocampal α7 nAChRs. Pregnant dams were stressed during their last week of gestation (days 14-21). Offspring were weaned at 21 days of age and assigned to same-sex same-diet cage-mates. In adulthood, offspring brains were collected and processed for quantitative autoradiography using 125I alpha-bungarotoxin (alpha-7 selective) ligand. Data analysis is near completion and the results will be presented at SBN. The results will have implications for mental illnesses with links to stress during the prenatal period such as schizophrenia, depressive disorders and anxiety.
P3.37 EFFECT OF PARITY GROUP ON NEURONAL ACTIVATION IN FEMALE MICE
Faye Raymond, Imelda Lopez, Marcia Caberera, Mike McCreary, Alex Kowalcyzk, Erin Lane, Kimberly D'Anna-Hernandez
Psychological Sciences | California State University San Marcos USA
Past research suggests that parity may contribute to hormonal responses in the brain. It has been hypothesized that lactating dams will experience lower neural activity when compared to virgin dams, likely as a result of sensitization to hormonal changes. These hormonal differences seen amongst the parity groups are operationalized as differences in neural activity; neural activity can be measured with cFos, an indirect marker. This study investigated the possible influences of parity group on neural activity, and its implications towards hormonal differences. Mice were divided into three groups; lactating dams (n= range of 4-10), sensitized virgins (n= range of 4-10), and naive virgins (n= range of 5-10). Mice brains were extracted and stained with cFos staining, then investigated utilizing Zeiss microscopy. Two distinct brain regions, the frontal cingulate cortex, and the anterior olfactory nucleus, were analyzed with a one-way ANOVA on IBM SPSS 22. While the differing parity groups experienced mean differences in these regions, the means were not statistically significantly different from one another. The anterior olfactory nucleus revealed no significant differences between naive virgins and sensitized virgins (p = .464); naive virgins and lactating dams (p= .993); and lactating dams and sensitized virgins (p= .559). The frontal cingulate cortex revealed no significant differences between naive virgins and sensitized virgins (p= .632); naive virgins and lactating dams (p= .999); and lactating dams and sensitized virgins (p= .662).
P3.38 EFFECTS OF ADOLESCENT CHRONIC MILD STRESS ON FEMALE WISTAR AND KYOTO RATS
Elizabeth Sahagun, Anna Hallowell, Brent Bachman, Kimberly P. Kinzig
Department of Psychological Sciences | Purdue University USA
Mood disorders are common and symptomatically challenging illnesses to treat. Despite years of research to understand underlying mechanisms and develop more effective treatments, numerous challenges still exist. There are many stress models and genetic strains used to study mood disorders, however the majority have been developed with adult males. This is problematic considering that affective disorders are more common in women, and many develop during adolescence. Additionally, studies have shown that there are fundamental behavioral and physiological differences between males and females in response to stressful stimuli, furthering a need to develop sex-specific paradigms to model the etiology of mood disorders in females. In this study, we tested stress susceptibility of Wistar (Ws) and Kyoto (Ky) female rats by using a chronic mild stress (CMS) paradigm during late adolescence (days 45-66). We measured body weight, food intake, and corticosterone levels during CMS to evaluate physiological effects. Immediately following CMS, animals underwent behavioral assessments of helplessness, anxiety, and anhedonia. Ky rat demonstrated endogenous behavioral and hormonal abnormalities that many symptom-presenting patients with depression exhibit, making them an appropriate model for testing therapeutics. Ws rats demonstrated more CMS-induced changes, indicating that Ws are more ideal for understanding the causal links between stress and susceptibility to mood disorders. These tests are repeated during late adulthood (~90 days) to determine long-term effects. The validation of these sex-specific models of mood disorders allow for more studies on the underlying mechanisms driving these disorders and ultimately contribute to the development of novel therapeutic strategies.
P3.39 OXYTOCIN ANTAGONISM INCREASES DEPRESSION-LIKE BEHAVIOR IN NULLIPAROUS BUT NOT POSTPARTUM RATS
Joanna L. Workman, Katie Parra, Joanna Medina, Alexandria Betit, Rose M. De Guzman
Department of Psychology | University at Albany, State University of New York USA
Oxytocin (OT) is a neuropeptide and has pleiotropic effects on maternal behavior, learning and memory, stress responses, and social behavior. During the postpartum period, oxytocin is released in a pulsatile pattern associated with suckling from offspring. Absence of nursing eliminates the intermittent peaks of oxytocin during the postpartum period. In humans, lower oxytocin release during breastfeeding postpartum was related with higher depression symptoms. Further, women who do not breastfeed are at greater risk for postpartum depression. In rodent models, OT has antidepressant like effects in the forced swim test and learned helplessness test. Thus, OT may be an important mediator of depression and depression-like behaviors in postpartum females. We sought to determine whether oxytocin receptor antagonism would alter depression-like behavior differently in reproductively naïve and early postpartum rats. We tested rats in the forced swim test (FST) on two consecutive days (FST 1: 15 min; FST 2: 5 min). Rats received oxytocin receptor antagonist (OTA; 3 mg/kg ip) or saline 30 min before testing in FST 2. OTA increased immobility in FST 2 in nulliparous rats, but not postpartum rats. Antagonism of oxytocin receptors differentially affects depression-like behavior in postpartum and nulliparous rats: OTA did not alter depressive-like behavior in the postpartum female but did increase depressive-like behavior in nulliparous rats. Using immunohistochemistry for c-Fos, we are currently identifying how OTA alters activation of brain regions involved in stress and affect in nulliparous and early postpartum rats.
P3.40 HYPOCRETIN ANTAGONISM'S INFLUENCE ON POSTPARTUM ANXIETY AND PUP RETRIEVAL IN MICE
Jace Kuske, Kimberly D'Anna-Hernandez
Psychological Sciences | California State University San Marcos USA
Postpartum anxiety is a detrimental condition that causes disruptions in maternal care to offspring and negatively impacts the health of a mother and her offspring. However, little is known about the underlying neurobiological causes of postpartum anxiety. High levels of hypocretin (HCRT), an arousal related peptide, has been associated with increased anxiety in non-lactating animals, and we know that there is increased HCRT activity during lactation in dams. Antagonizing HCRT receptor 1 (HCRTr1) decreases anxiety in non-lactating rodents, so we wanted to explore if this was true in lactating mice. Using two doses of SB-334867 (10 mg/kg, 30 mg/kg), a HCRTr1 antagonist, and a modified light/dark box protocol to include a pup retrieval task, we saw that HCRTr1 antagonism increased anxiety behaviors and decreased pup retrieval. Dams given a low dose spent less time in the light (M = 119.06, SEM = 25.54) compared to our vehicle group (M = 217.13, SEM = 24.70), and dams given a high dose (M = 11.53, SEM = 2.94) entered the light less often than our vehicle group (M = 21.87, SEM = 2.12). Additionally, dams given the high dose retrieved less pups (M = 0.13, SEM = 0.13) than our vehicle control group (M = 1.00, SEM = 0.26). These results indicate that HCRT's role on anxiety behaviors could differ in the postpartum period compared to non-lactating mice, and that HCRT antagonism impairs maternal behaviors like pup retrieval.
P3.41 UNORTHODOX CIRCADIAN RHYTHMS IN MICE LACKING COMMENSAL MICROBES
Kenneth G. Onishi1,2, Vanessa Leone3, Andrew C. Maneval1,2, Carina Elvira1,2, J.P. Riggle1,2, Betty R. Theriault4, Eugene B. Chang3, Brian J. Prendergast1,2
1Psychology Department, 2Institute for Mind and Biology, 3Medicine, 4Surgery | University of Chicago
Present in all living organisms, from prokaryotes to vertebrates, circadian clocks impart daily temporal structure in behavior. Cellular circadian oscillators have periods of ~24 h and are mutually coupled to one another; a hierarchical network structure allows them to function as pacemakers, synchronizing period and phase at the organ- and organismal-level. Here we examine how the trillions of microbes that co-inhabit the body influence basic aspects of brain function and behavior. The host circadian system sustains daily rhythms in physiology (e.g., body temperature), behavior (e.g., locomotor activity, ingestive behavior) and brain function (learning, affective state), but also maintains daily rhythms in the abundance, membership, and function of symbiotic microbes in the gut ecosystem. Emerging evidence indicates that communication between the host circadian system and the gut microbiota is bidirectional, but the extent to which the trillions of gut microbes impact the generation and expression of organismal circadian rhythms has not been directly examined. To examine the impact of the gut microbiota on the host circadian network, we developed a novel, non-invasive, wireless method for continuous assessment of circadian rhythms in spontaneous home cage locomotor activity (LMA) and core body temperature (Tb) in freely-behaving germ-free (GF) mice housed in sterile flexible-film isolators as compared to specific pathogen free (SPF) mice harboring a full microbial community housed under nearly identical conditions. In the presence and absence of gut microbiota, circadian rhythms in LMA and Tb were examined.
P3.42 MATERNAL EXPERIENCE-DEPENDENT AUDITORY CORTICAL PLASTICITY IS CIRCUIT- AND STIMULUS-SPECIFIC AND REQUIRES METHYL-CpG-BINDING PROTEIN 2 (MECP2) IN MICE
Billy Y. B. Lau1,2, Keerthi Krishnan1,2, Z. Josh Huang1, Stephen D. Shea1
1Cold Spring Harbor Laboratory, New York USA, 2Dept. of Biochemistry & Cellular and Molecular Biology, University of Tennessee at Knoxville, USA
Cohabitation of adult nulliparous mice with pups and mother induces maternal behavior in them in a hormone-independent manner. Such non-hormonal factors are thought to be important in mediating plasticity, likely through chromatin remodeling of specific neural circuitry (Stolzenberg and Champagne, 2016). We have previously shown that Methyl CpG-binding protein 2 (MECP2), a chromatin remodeling protein and gene regulator, in the auditory cortex is essential for efficient pup retrieval task in a learned maternal behavior paradigm. Furthermore, we showed atypical plasticity in parvalbumin+ (PV+) GABAergic neurons of nulliparous MECP2- heterozygous surrogate mice (Hets), compared to wild-type littermate controls (WT) (Krishnan, Lau et al, 2017). These results led us to speculate that Hets had atypical auditory processing phenotype. Here we show that maternal experience in WT triggers PV+-mediated disinhibition of auditory responses in deep-layer pyramidal neurons that is selective for behaviorally-relevant pup vocalizations, by performing extracellular recordings in awake mice. These neurons also exhibit sharpened tuning for pup vocalizations following maternal experience. All of these neuronal changes are abolished in Hets, suggesting that they are essential for efficient execution of pup retrieval task. Taken together, our data suggests that MECP2 regulates the timing of plasticity through PV+ neuronal networks, which ultimately affects adult plasticity essential for learning and execution of efficient pup retrieval task.
P3.43 RECONSTRUCTING VASOPRESSIN PATHWAYS IN THE BRATTLEBORO RAT
Kelcie C. Schatz1, Lauren M. Brown1, Abigal R. Barrett1, Lena C. Roth2, Valerie Grinevich2,3,4, Matthew J. Paul1
1Department of Psychology, University at Buffalo, SUNY, NY, USA; 2Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Heidelberg, Germany; 3Schaller Group on Neuropeptides, German Cancer Research Center, Heidelberg, Germany; 4Central Institute of Mental Health, Mannheim, Germany
The neuropeptide, arginine vasopressin (AVP), has been implicated in a number of neurodevelopmental disorders that impact social and emotional development (e.g., autism and ADHD). Nevertheless, we do not understand how AVP modulates behavioral development or how its altered function contributes to neurodevelopmental disorders. The Brattleboro rat, which lacks AVP due to a mutation in the Avp gene, is an ideal model to study the impact of life-long AVP disruption. Brattleboro rats suffer from diabetes insipidus – excessive drinking and urination due to the loss of AVP action on the kidney. We have found that adolescent Brattleboro rats also exhibit atypical social behavior associated with decreased arousal. To determine the pathway responsible, we developed a viral-rescue approach to restore AVP within a single pathway, beginning with the paraventricular nucleus of the hypothalamus (PVN). Infusion of a recombinant adeno-associated virus containing a functional Avp gene and promoter rescued AVP within magnocellular cells of the PVN and fiber projections to the posterior pituitary and limbic structures. Water intake was markedly reduced, ameliorating the symptoms of diabetes insipidus, but behavioral arousal was unaffected. These findings indicate that the hyporaoused phenotype of adolescent Brattleboro rats is not due to the loss of AVP function in PVN magnocellular cells or a side effect of diabetes insipidus. Instead, parvocellular pathways likely underlie AVP regulation of arousal during adolescence. More broadly, these experiments illustrate a novel approach that “reconstructs” individual pathways in genetic mutant models to assess their role in behavioral phenotypes.
P3.44 RNA-SEQ REVEALS DISTINCT REGIONAL TESTOSTERONE-SENSITVE AND INSENSITIVE PATTERNS IN SEXUALLY DIMOMROPHIC GENE EXPRESSION IN THE BRAIN OF JAPANESE QUAIL
Brett C. Mommer1†, Rodrigo Gularte Mérida2*, Wouter Coppieters3, Charlotte A. Cornil1
1GIGA – Neurosciences, 2Unit of Animal Genomics, 3GIGA – Genomics Platform, Université de Liège, Belgium, †School of Public Health, University of Washington USA, *Sloan Memorial Kettering Cancer Center USA
Male and female Japanese quail display distinct physiology and behavior as a result of genetic differences and differential exposure to hormones during development and adulthood. The genes underlying these differences are largely unknown, especially in birds. The present study investigated transcriptomic sex differences in three brain regions (medial preoptic nucleus [POM], ventromedial nucleus of the hypothalamus [VMN] and nucleus taeniae of the amygdala [TnA]) of adult male and female quail left gonadally intact or gonadectomized and treated with testosterone (GDX+T). Overall, POM showed the largest number of differentially expressed genes (DEG). As expected, some DEG turned out to be sensitive to testosterone treatment while others were insensitive, but GDX+T also uncovered DEG that were not different in intact subjects suggesting that T (or ovarian hormones) actively “repress” some otherwise sexually-dimorphic genes. Some DEG were identified in only one nucleus and tended to be more T-sensitive, particularly in the POM which, surprisingly, had female-bias from autosomes and male-bias from the Z chromosome. In contrast other DEG, most of them T-insensitive, were common to several nuclei. DEG common to POM and VMN were most abundant, being mostly male-biased and located on sex chromosomes. Most DEG common to all nuclei are only expressed in females suggesting they are located on chromosome W. Three patterns of DEG thus emerge in response to testosterone: T-sensitive, T–insensitive, and DEG normally repressed by T, each depending on neuroanatomical and chromosomal location, representing sets of candidate genes that could explain fundamental behavioral sex differences in adult birds.
P3.45 NOVEL APPROACHES FOR NEUROTOXICOLOGY: USE OF THE PRAIRIE VOLE TO ASSESS THE IMPACT OF DEVELOPMENTAL FLAME RETARDANT EXPOSURE ON SOCIAL BEHAVIORS
Sagi Gillera1, William Marinello1, Brian Horman1, Ruta Grinceviciute3, Heather Patisaul1,2
1Department of Biological Sciences, 2Center for Human Health and the Environment, NC State University USA; 3Department of Biological Sciences, University of Texas at El Paso USA
The rapidly rising incidence of neurodevelopmental disorders is raising speculation that environmental contaminants may be contributory. Firemaster 550 (FM550) is one of the most prevalent flame-retardant (FR) mixtures used in foam-based furniture and baby products. We and others have published evidence of developmental neurotoxicity and sex specific effects of FM550 on anxiety-like and exploratory behaviors in rats and zebrafish. To test the hypothesis that FM550 affects social behavior, we investigated the impact of perinatal FM550 on a range of social behaviors in prairie voles. Virtually unknown to toxicologists, the prairie vole (Microtus ochrogaster) is a uniquely valuable model organism for examining environmental impacts on sociality because it is spontaneously prosocial and displays pair bonding behaviors. Dams were exposed to three, human relevant doses of FM500 via subcutaneous injections throughout gestation, and pups were then exposed daily until weaning. Adult offspring of both sexes were then subjected to multiple tasks including open field, novel object recognition, and partner preference. Effects were dose responsive and sex specific, with females more affected. Behavioral effects included elevated anxiety, decreased social interaction, decreased exploratory motivation, and altered social preference for novel versus familiar animals. FM550 also sex-specifically affected pair bond formation, with a loss of preference in males. Our studies demonstrate the utility of the prairie vole for investigating the impact of chemical exposures on sociality and attachment. The data support the hypothesis that developmental FR exposure impacts the social brain and future studies will probe the possible mechanisms by which these effects arise.
P3.46 EFFECTS OF EARLY LIFE STRESS ON MCC AND DOPAMINE RECEPTOR EXPRESSION
Adriana Pero, Michelle Tomaszycki
Lafayette College USA
Zebra finches are an excellent model of learning and memory. Developmental nutritional stress (NS), a model for early life adversity, is known to cause learning deficits in male zebra finches, evidenced by reduced song complexity. Although the neural basis of the NS learning deficit is not well understood, genes likely play a role. One candidate is the gene coding for the enzyme 3-methylcrotonyl carboxylase (MCC), which is necessary for leucine catabolism. MCC deficiency is known to cause cognitive deficits and learning disabilities, positing that MCC is important for learning. Additionally, dopamine plays an important role in learning. In male zebra finches, MCC and dopamine receptors (D1a and D2) are both present in the song-learning pathway, and NS may cause learning deficits by altering expression of dopamine receptors and MCC in the song pathway. Female zebra finches exposed to NS were unable to choose males on the basis of song quality, suggesting that NS also causes learning deficits in females. However, not much is known about the presence of MCC and dopamine in the learning pathways in female zebra finches. The present study will investigate the extent to which NS reduces MCC and dopamine receptor (D1A and D2) expression in song and auditory pathways of NS zebra finches of males and females. By examining the effect of NS on MCC and dopamine receptor expression, our results will help elucidate the role of MCC and dopamine in learning, and also elucidate the neural correlates of early life adversity.