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Oxytocin depolarizes fast‐spiking hilar interneurons and induces GABA release onto mossy cells of the rat dentate gyrus
Author(s) -
Harden Scott W.,
Frazier Charles J.
Publication year - 2016
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.22595
Subject(s) - neuroscience , dentate gyrus , gabaergic , granule cell , oxytocin , inhibitory postsynaptic potential , psychology , chemistry , hippocampus
Delivery of exogenous oxytocin (OXT) to central oxytocin receptors (OXT‐Rs) is currently being investigated as a potential treatment for conditions such as post‐traumatic stress disorder (PTSD), depression, social anxiety, and autism spectrum disorder (ASD). Despite significant research implicating central OXT signaling in modulation of mood, affect, social behavior, and stress response, relatively little is known about the cellular and synaptic mechanisms underlying these complex actions, particularly in brain regions which express the OXT‐R but lie outside of the hypothalamus (where OXT‐synthesizing neurons reside). We report that bath application of low concentrations of the selective OXT‐R agonist Thr4,Gly7‐OXT (TGOT) reliably and robustly drives GABA release in the dentate gyrus in an action potential dependent manner. Additional experiments led to identification of a small subset of small hilar interneurons that are directly depolarized by acute application of TGOT. From a physiological perspective, TGOT‐responsive hilar interneurons have high input resistance, rapid repolarization velocity during an action potential, and a robust afterhyperpolarization. Further, they fire irregularly (or stutter) in response to moderate depolarization, and fire quickly with minimal spike frequency accommodation in response to large current injections. From an anatomical perspective, TGOT responsive hilar interneurons have dense axonal arborizations in the hilus that were found in close proximity with mossy cell somata and/or proximal dendrites, and also invade the granule cell layer. Further, they have primary dendrites that always extend into the granule cell layer, and sometimes have clear arborizations in the molecular layer. Overall, these data reveal a novel site of action for OXT in an important limbic circuit, and represent a significant step towards better understanding how endogenous OXT may modulate flow of information in hippocampal networks. © 2016 Wiley Periodicals, Inc.