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      Oxytocin via oxytocin receptor excites neurons in the endopiriform nucleus of juvenile mice

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          Abstract

          The neuropeptide oxytocin (OXT) modulates social behaviors across species and may play a developmental role for these behaviors and their mediating neural pathways. Despite having high, stable levels of OXT receptor (OXTR) ligand binding from birth, endopiriform nucleus (EPN) remains understudied. EPN integrates olfactory and gustatory input and has reciprocal connections with several limbic areas. Because the role of OXTR signaling in EPN is unknown, we sought to provide anatomical and electrophysiological information about OXTR signaling in mouse EPN neurons. Using in situ hybridization, we found that most EPN neurons co-express Oxtr mRNA and the marker for VGLUT1, a marker for glutamatergic cells. Based on high levels of OXTR ligand binding in EPN, we hypothesized that oxytocin application would modulate activity in these cells as measured by whole-cell patch-clamp electrophysiology. Bath application of OXT and an OXTR specific ligand (TGOT) increased the excitability of EPN neurons in wild-type, but not in OXTR-knockout (KO) tissue. These results show an effect of OXT on a mainly VGLUT1+ cell population within EPN. Given the robust, relatively stable OXTR expression in EPN throughout life, OXTR in this multi-sensory and limbic integration area may be important for modulating activity in response to an array of social or other salient stimuli throughout the lifespan and warrants further study.

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          Most cited references73

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          A gene expression atlas of the central nervous system based on bacterial artificial chromosomes.

          The mammalian central nervous system (CNS) contains a remarkable array of neural cells, each with a complex pattern of connections that together generate perceptions and higher brain functions. Here we describe a large-scale screen to create an atlas of CNS gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines that offer experimental access to CNS regions, cell classes and pathways. We illustrate the use of this atlas to derive novel insights into gene function in neural cells, and into principal steps of CNS development. The atlas, library of BAC vectors and BAC transgenic mice generated in this screen provide a rich resource that allows a broad array of investigations not previously available to the neuroscience community.
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            Social reward requires coordinated activity of accumbens oxytocin and 5HT

            Social behaviors in species as diverse as honey bees and humans promote group survival but often come at some cost to the individual. Although reinforcement of adaptive social interactions is ostensibly required for the evolutionary persistence of these behaviors, the neural mechanisms by which social reward is encoded by the brain are largely unknown. Here we demonstrate that in mice oxytocin (OT) acts as a social reinforcement signal within the nucleus accumbens (NAc) core, where it elicits a presynaptically expressed long-term depression of excitatory synaptic transmission in medium spiny neurons. Although the NAc receives OT receptor-containing inputs from several brain regions, genetic deletion of these receptors specifically from dorsal raphe nucleus, which provides serotonergic (5-HT) innervation to the NAc, abolishes the reinforcing properties of social interaction. Furthermore, OT-induced synaptic plasticity requires activation of NAc 5-HT1b receptors, the blockade of which prevents social reward. These results demonstrate that the rewarding properties of social interaction in mice require the coordinated activity of OT and 5-HT in the NAc, a mechanistic insight with implications for understanding the pathogenesis of social dysfunction in neuropsychiatric disorders such as autism.
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              Oxytocin Enables Maternal Behavior by Balancing Cortical Inhibition

              Oxytocin is important for social interactions and maternal behavior. However, little is known about when, where, and how oxytocin modulates neural circuits to improve social cognition. Here we show how oxytocin enables pup retrieval behavior in female mice by enhancing auditory cortical pup call responses. Retrieval behavior required left but not right auditory cortex, was accelerated by oxytocin in left auditory cortex, and oxytocin receptors were preferentially expressed in left auditory cortex. Neural responses to pup calls were lateralized, with co-tuned and temporally-precise excitatory and inhibitory responses in left cortex of maternal but not pup-naive adults. Finally, pairing calls with oxytocin enhanced responses by balancing the magnitude and timing of inhibition with excitation. Our results describe fundamental synaptic mechanisms by which oxytocin increases the salience of acoustic social stimuli. Furthermore, oxytocin-induced plasticity provides a biological basis for lateralization of auditory cortical processing.
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                Author and article information

                Contributors
                LBiggs@neuro.fsu.edu
                EHammock@fsu.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                6 July 2022
                6 July 2022
                2022
                : 12
                : 11401
                Affiliations
                GRID grid.255986.5, ISNI 0000 0004 0472 0419, Program in Neuroscience, Department of Psychology, , Florida State University, ; Tallahassee, FL 32306 USA
                Author information
                https://orcid.org/0000-0001-7700-6599
                http://orcid.org/0000-0001-7668-745X
                Article
                15390
                10.1038/s41598-022-15390-5
                9259672
                35794163
                01630f2d-74ca-4b6b-8de8-8ff9c98c3afa
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 January 2022
                : 23 June 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: MH114994
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                Uncategorized
                neuroscience,neural circuits,neuronal physiology,social neuroscience
                Uncategorized
                neuroscience, neural circuits, neuronal physiology, social neuroscience

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