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Campos-Lira, E.

Publications and source records attributed to Campos-Lira, E..

2 recordsLinked to original sources

A vasopressin circuit that modulates sex-specific social interest and anxiety-like behavior in mice

One of the largest sex differences in brain neurochemistry is the male-biased expression of the neuropeptide arginine vasopressin (AVP) within the vertebrate social brain. Despite the long-standing implication of AVP in social and anxiety-like behavior, the precise circuitry and anatomical substrate underlying its control are still poorly understood. By employing optogenetic manipulation of AVP cells within the bed nucleus of the stria terminalis (BNST), we have unveiled a central role for these cells in promoting social investigation, with a more pronounced role in males relative to females. These cells facilitate male social investigation and anxiety-like behavior through their projections to the lateral septum (LS), an area with the highest density of sexually-dimorphic AVP fibers. Blocking the vasopressin 1a receptor (V1aR) in the LS eliminated stimulation-mediated increases in these behaviors. Together, these findings establish a distinct BNST AVP [->] LS V1aR circuit that modulates sex-specific social interest and anxiety-like behavior. Significance StatementThe function of sex differences in the brain is poorly understood. Here we test the function of one of the most consistently found sex differences in vertebrate brains, the male-biased vasopressin projections from the bed nucleus of the stria terminalis. Using optogenetic techniques, we demonstrate that these cells and their projection to the lateral septum are much more important in driving male than female social investigation. These studies make a strong contribution to understanding how sexually dimorphic circuitry controls social behavior.

neuroscience↗

Vasopressin acts as a synapse organizer in limbic regions by boosting PSD95 and GluA1 expression

Hypothalamic arginine vasopressin (AVP)-containing magnocellular neurosecretory neurons (AVPMNN) emit collaterals to synaptically innervate limbic regions influencing learning, motivational behaviour, and fear responses. Here, we characterize the dynamics of expression changes of two key determinants for synaptic strength, the postsynaptic density (PSD) proteins AMPAR subunit GluA1 and PSD scaffolding protein 95 (PSD95), in response to in vivo manipulations of AVPMNN neuronal activation state, or exposure to exogenous AVP ex vivo. Both long term water deprivation in vivo, which powerfully upregulates AVPMNN metabolic activity, and exogenous AVP application ex vivo, in brain slices, significantly increased GluA1 and PSD95 expression measured by western blot, in brain regions reportedly receiving direct ascending innervations from AVPMNN (i.e., ventral hippocampus, amygdala and lateral habenula). In contrast, the visual cortex, a region not observed to receive AVPMNN projections, showed no such changes. Ex vivo application of V1a and V1b antagonists to ventral hippocampal slices ablated the AVP stimulated increase in postsynaptic protein expression measured by western blot. Using a modified expansion microscopy technique, we were able to quantitatively assess the significant augmentation of PSD95 and GLUA1 densities in subcellular compartments in locus coeruleus tyrosine hydroxylase immunopositive fibres, adjacent to AVP axon terminals. Our data strongly suggest that the AVPMNN ascending system plays a role in the regulation of the excitability of targeted neuronal circuits through upregulation of key post-synaptic density proteins corresponding to excitatory synapse. Supported by grantsUNAM-DGAPA-PAPIIT-IN200121 & CONACYT-CB-238744 (LZ); CONACYT A1-S-8731 (LIE); MH002386, NIMH, NIH, USA (LEE)

neuroscience↗