Biology subjects

Trainor, B. C.

Publications and source records attributed to Trainor, B. C..

7 recordsLinked to original sources

bioRxiv2025

Oxytocin neurons in the anterior and posterior paraventricular nucleus have distinct behavioral functions and electrophysiological profiles

Oxytocin is a neuropeptide that can promote or inhibit affiliative social behaviors. Recent evidence suggests that these diverse effects are mediated by distinct oxytocin receptor-expressing neurons. An outstanding question is whether these behavioral effects are also driven by distinct or overlapping populations of oxytocin-producing neurons. The paraventricular nucleus (PVN) of the hypothalamus is a major source of oxytocin and sends projections to the mesolimbic dopamine system and extended amygdala. Previous work found that social defeat increased oxytocin neuron activity in the anterior PVN (aPVN) but not posterior PVN (pPVN). We reduced oxytocin synthesis with antisense morpholino oligonucleotides in either anterior or posterior PVN in California mice (Peromyscus californicus), a strong model system for studying effects of social stress on brain function and behavior. Antisense morpholinos in aPVN had no effect on behavior in unstressed females but increased social approach and reduced social vigilance in females exposed to social defeat stress. In pPVN, antisense morpholinos reduced social approach in unstressed male and female California mice. We then used OxtCre mice to compare electrophysiological profiles of oxytocin in aPVN and pPVN with a population of oxytocin neurons in the bed nucleus of the stria terminalis (BNST). Oxytocin neurons in aPVN and BNST had higher post-synaptic events and responded more strongly to current injections than oxytocin neurons in pPVN, though they had similar excitatory and inhibitory input balance at the observed resting membrane potential. These findings shed light onto functional and physiological heterogeneity of PVN oxytocin neurons. Our results suggest that context dependent effects of oxytocin are mediated by different populations of oxytocin neurons.

neuroscience↗

bioRxiv2025

CRISPR-mediated knockdown of oxytocin receptor in extended amygdala reduces stress-induced social avoidance and vigilance

Oxytocin receptors (OTRs) within the extended amygdala and nucleus accumbens (NAc) have been implicated in modulating social behaviors, particularly following stress. The effects of OTR could be mediated by modulating the activity of pre-synaptic axon terminals or via receptors in post-synaptic neurons or glia. Using a viral-mediated CRISPR/Cas9 gene editing system in female California mice (Peromyscus californicus), we selectively knocked down OTR in the anteromedial bed nucleus of the stria terminalis (BNST) or NAc to examine their roles modulating social approach and vigilance behaviors. Knockdown of OTR in the BNST attenuated stress-induced decreases of social approach and had less robust effects on vigilance when interacting with a target mouse behind a wire barrier. In this large arena, where mice could control their proximity to a target mouse, BNST OTR knockdown also increased investigation of a non-social stimulus (empty cage). Behavioral effects of BNST OTR knockdown were weaker in the small arena where focal mice physically interacted with target mice. Interestingly, OTR knockdown in the NAc, reduced stress-induced social vigilance without affecting social approach. These effects could mediated altered encoding of socially aversive experiences, as knockdown manipulations were performed before stress exposure. Together, these results highlight effects of local OTR on social behavior are region-specific.

neuroscience↗

bioRxiv2023

Sex differences in responses to aggressive encounters among California mice

Despite how widespread female aggression is across the animal kingdom, there remains much unknown about its neuroendocrine mechanisms, especially in females that engage in aggression outside the peripartum period. Although the impact of experience in aggressive encounters on steroid hormone responses have been described, little is known about the impact of these experiences on female behavior or their neuropeptide responses. In this study, we compared behavioral responses in both male and female adult California mice based on if they had 0, 1, or 3 aggressive encounters using a modified resident intruder paradigm. We measured how arginine vasopressin and oxytocin cells in the paraventricular nucleus responded to aggression using c-fos immunohistochemistry. We saw that both sexes disengaged with intruders with repeated aggressive encounters, but that on the final day of testing females were most likely to freeze when they encountered intruders compared to no aggression controls - which was not significant in males. Finally, we saw that percent of arginine vasopressin and c-fos co-localizations in the posterior region of the paraventricular nucleus increased in males who fought compared to no aggression controls. No difference was observed in females. Overall, there is evidence that engaging in aggression induces stress responses in both sexes, and that females may be more sensitive to the effects of fighting.

neuroscience↗

bioRxiv2021

Environmental enrichment delays the development of stereotypic behavior and reduces variability in behavioral experiments using California mice (Peromyscus californicus).

Domesticated mice and rats have shown to be powerful model systems for biomedical research, but there are cases in which the biology of species is a poor match for the hypotheses under study. The California mouse (Peromyscus californicus) has unique physiological and behavioral traits and has emerged as a powerful model for studying sex differences in the biology of psychiatric disease, which is particularly relevant considering the new NIH guidelines that require the inclusion of sex as a biological variable. Despite its growing role in preclinical research, there is a lack of studies assessing species-specific housing needs, which presents a challenge for research facilities seeking to ensure good welfare and obtaining high-quality experimental data. Indeed, captive California mice present a high prevalence of stereotypic backflipping behavior, a common consequence of suboptimal housing and a potential source of experimental outcome variability. Using three different cage systems, the present studies show that increasing housing space as well as social and environmental complexity can delay the development of stereotypic behavior in male and female California mice. Critically, this reduction in stereotypy is accompanied by increased effect sizes of stress in an established model for social anxiety. These results suggest that increased cage size and enrichment could enhance welfare in California mice while simultaneously increasing the quality of behavioral experiments.

animal behavior and cognition↗

bioRxiv2020

Pubertal androgens reduce the effects of social stress on anxiety-related behaviors in California mice

Anxiety disorders are more common in women than men, and this difference arises during puberty. Increased secretion of gonadal hormones during puberty influences brain structure and function, but the extent to which hormones modulate anxiety-related brain circuits is unclear. The slow developing California mouse (Peromyscus californicus) is an ideal species for studying the effects of hormones on brain function during adolescence. In adults social defeat stress reduces social approach and increases vigilance in females but not males. Here we show this sex difference is absent in juvenile mice, and that prepubertal castration sensitizes adult males to social defeat. Since adult castration has no effect on stress sensitivity, our data show that gonadal hormones act during puberty to program behavioral responses to stress later in life. In adults, calcium imaging in the medioventral bed nucleus of the stria terminalis shows that threatening social contexts increase calcium transients. Furthermore, prepubertal castration generalizes these responses to less threatening social contexts. Prepubertal treatment with the non-aromatizable androgen dihydrotestosterone acts in males and females to reduce sensitivity to social defeat in adults. Together, these data indicate activation of androgen receptors during puberty are critical for programing behavioral responses to stress in adulthood, highlighting a possible mechanism contributing to sex differences in anxiety. Significance StatementPuberty is a key period when sex differences in anxiety emerges. Gonadal hormone release increases during this time but it is largely unknown how they impact brain circuits and behavior. We show that androgens play a key role in programming behavioral responses to social defeat stress. The bed nucleus of the stria terminalis responds to social threats and these responses are more generalized in males without gonadal hormone exposure during puberty. Our findings highlight the importance of pubertal androgens in determining adult behavioral responses to social stress.

developmental biology↗

bioRxiv2020

Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance

Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a social stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knock-down prevented stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naive mice increased social vigilance and reduced social approach. These results show that a population of extra-hypothalamic oxytocin neurons play a key role in controlling stress-induced social anxiety behaviors.

neuroscience↗

bioRxiv2018

Histone deacetylase inhibitor treatment promotes spontaneous caregiving behavior in C57BL/6J male mice

Whereas the majority of mammalian species are uni-parental with the mother solely provisioning care for young conspecifics, fathering behaviors can emerge under certain circumstances. For example, a great deal of individual variation in response to young pups has been reported in multiple inbred strains of laboratory male mice. Further, sexual experience and subsequent cohabitation with a female conspecific can induce caregiving responses in otherwise indifferent, fearful or aggressive males. Thus, a highly conserved parental neural circuit is likely present in both sexes, however the extent to which infants are capable of accessing this circuit may vary. In support of this idea, fearful or indifferent responses toward pups in female mice are linked to greater immediate early gene (IEG) expression in a fear/defensive circuit involving the anterior hypothalamus than in an approach/attraction circuit involving the ventral tegmental area. However, experience with infants, particularly in combination with histone deacetylase inhibitor (HDACi) treatment, can reverse this pattern of neuronal activation and behavior. Thus, HDACi treatment may increase the transcription of primed/poised genes that play a role in the activation and selection of a maternal approach circuit in response to pup stimuli. Here, we asked whether HDACi treatment would impact behavioral response selection and associated IEG expression changes in virgin male mice that are capable of ignoring, attacking or caring for pups. Our results indicate that systemic HDACi treatment induces spontaneous caregiving behavior in non-aggressive male mice and alters the pattern of pup-induced IEG expression across a fear/defensive neural circuit.

neuroscience↗