skip to main content


Title: Extrahypothalamic 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 stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knockdown prevented social 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 naïve mice increased social vigilance and reduced social approach. These results show that a population of extrahypothalamic oxytocin neurons plays a key role in controlling stress-induced social anxiety behaviors.  more » « less
Award ID(s):
1810898
NSF-PAR ID:
10298547
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
117
Issue:
42
ISSN:
0027-8424
Page Range / eLocation ID:
26406 to 26413
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    Galanin is a peptide that regulates pituitary hormone release, feeding, and reproductive and parental care behaviors. In teleost fish, increased galanin expression is associated with territorial, reproductively active males. Prior transcriptome studies of the plainfin midshipman (Porichthys notatus), a highly vocal teleost fish with two male morphs that follow alternative reproductive tactics, show that galanin is upregulated in the preoptic area‐anterior hypothalamus (POA‐AH) of nest‐holding, courting type I males during spawning compared to cuckolding type II males. Here, we investigate possible differences in galanin immunoreactivity in the brain of both male morphs and females with a focus on vocal‐acoustic and neuroendocrine networks. We find that females differ dramatically from both male morphs in the number of galanin‐expressing somata and in the distribution of fibers, especially in brainstem vocal‐acoustic nuclei and other sensory integration sites that also differ, though less extensively, between the male morphs. Double labeling shows that primarily separate populations of POA‐AH neurons express galanin and the nonapeptides arginine‐vasotocin or isotocin, homologues of mammalian arginine vasopressin and oxytocin that are broadly implicated in neural mechanisms of vertebrate social behavior including morph‐specific actions on vocal neurophysiology in midshipman. Finally, we report a small population of POA‐AH neurons that coexpress galanin and the neurotransmitter γ‐aminobutyric acid. Together, the results indicate that galanin neurons in midshipman fish likely modulate brain activity at a broad scale, including targeted effects on vocal motor, sensory and neuroendocrine systems; are unique from nonapeptide‐expressing populations; and play a role in male‐specific behaviors.

     
    more » « less
  2. Mus musculus enters a torpid state in response to caloric restriction in sub-thermoneutral ambient temperatures. This torpid state is characterized by an adaptive and controlled decrease in metabolic rate, heart rate, body temperature, and activity. Previous research has identified the paraventricular nucleus (PVN) within the hypothalamus, a region containing oxytocin neurons, as a location that is active during torpor onset. We hypothesized that oxytocin neurons within the PVN are part of this neural circuit and that activation of oxytocin neurons would deepen and lengthen torpor bouts. We report that activation of oxytocin neurons alone is not sufficient to induce a torpor-like state in the fed mouse, with no significant difference in body temperature or heart rate upon activation of oxytocin neurons. However, we found that activation of oxytocin neurons prior to the onset of daily torpor both deepens and lengthens the subsequent bout, with a 1.7 ± 0.4 °C lower body tempera- ture and a 135 ± 32 min increase in length. We therefore conclude that oxytocin neurons are involved in the neural circuitry controlling daily torpor in the mouse. 
    more » « less
  3. Social information gathering is a complex process influenced by neuroendocrine-modulated neural plasticity. Oxytocin (OXT) is a key regulator of social decision-making processes such as information gathering, as it contextually modulates social salience and can induce long-term structural plasticity, including neurogenesis. Understanding the link between OXT-induced plasticity and communicative awareness is crucial, particularly because OXT is being considered for treatment of social pathologies. We investigated the role of chronic OXT-dependent plasticity in attention to novel social information by manipulating the duration of time following cessation of intranasal treatment to allow for the functional integration of adult-born neurons resulting from OXT treatment. Following a 3-week delay, chronic intranasal OXT (IN-OXT) increased approach behavior of both female and male mice towards aggressive vocal playbacks of two unseen novel conspecifics, while no effect was observed after a 3-day delay. Immature neurons increased in the ventral hippocampus of females and males treated with chronic IN-OXT after the 3-week delay, indicating a potential association between ventral hippocampal neurogenesis and approach/acoustic eavesdropping. The less the mouse approached, the higher the level of neurogenesis. Contrary to expectations, the correlation between ventral hippocampal neurogenesis and approach behavior was not affected by IN-OXT, suggesting that other plasticity mechanisms underlie the long-term effects of chronic OXT on social approach. Furthermore, we found a negative correlation between ventral hippocampal neurogenesis and freezing behavior. Overall, our results demonstrate that chronic IN-OXT-induced long-term plasticity can influence approach to vocal information and we further reinforced the link between neurogenesis and anxiety. 
    more » « less
  4. Abstract

    The transient receptor potential cation channel 2 (TRPC2) conveys pheromonal information from the vomeronasal organ (VNO) to the brain. Both male and female mice lacking this gene show altered sex‐typical behavior as adults. We asked whether TRPC2, highly expressed in the VNO, normally participates in the development of VNO‐recipient brain regions controlling mounting and aggression, two behaviors affected by TRPC2 loss. We now report significant effects of TRPC2 loss in both the posterodorsal aspect of the medial amygdala (MePD) and ventromedial nucleus of the hypothalamus (VMH) of male and female mice. In the MePD, a sex difference in neuron number was eliminated by the TRPC2 knockout (KO), but the effect was complex, with fewer neurons in therightMePD of females, and fewer neurons in theleftMePD of males. In contrast, MePD astrocytes were unaffected by the KO. In the ventrolateral (vl) aspect of the VMH, KO females were like wildtype (WT) females, but TRPC2 loss had a dramatic effect in males, with fewer neurons than WT males and a smaller VMHvl overall. We also discovered a glial sex difference in VMHvl of WTs, with females having more astrocytes than males. Interestingly, TRPC2 lossincreasedastrocyte number in males in this region. We conclude that TRPC2 normally participates in the sexual differentiation of the mouse MePD and VMHvl. These changes in two key VNO‐recipient regions may underlie the effects of the TRPC2 KO on behavior.

     
    more » « less
  5. Abstract Introduction

    In humans, satisfying sexual activity within a pair‐bond plays a significant role in relationship quality and maintenance, beyond reproduction. However, the neural and genetic correlates for this basic species‐supporting function, in response to a pair‐bonded partner, are unknown.

    Methods

    We examined the neural correlates of oxytocin‐ (Oxtrrs53576) and vasopressin‐ (Avpr1a rs3) receptor genotypes with sexual satisfaction and frequency, among a group of individuals in pair‐bonds (M relationship length = 4.1 years). Participants were scanned twice (with functional MRI), about 1‐year apart, while viewing face images of their spouse and a familiar, neutral acquaintance.

    Results

    Sex satisfaction scores showed significant interactions withOxtrandAvprvariants associated with social behaviors in a broad network of regions involved in reward and motivation (ventral tegmental area, substantia nigra [SN], and caudate), social bonding (ventral pallidum), emotion and memory (amygdala/hippocampus), hormone control (hypothalamus); and somatosensory and self‐other processing (SII, frontal, and temporal lobe). Sexual frequency interactions also showed activations in the SN and paraventricular hypothalamus forAvpr, and the prefrontal cortex forOxtr.

    Conclusions

    Satisfying sexual activity in pair‐bonds is associated with activation of subcortical structures that support basic motivational and physiological processes; as well as cortical regions that mediate complex thinking, empathy, and self‐other processes highlighting the multifaceted role of sex in pair‐bonds.OxtrandAvprgene variants may further amplify both basic and complex neural processes for pair‐bond conservation and well‐being.

     
    more » « less