1. Neurexin-3 defines synapse- and sex-dependent diversity of GABAergic inhibition in ventral subiculum
- Author
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Seng C, Boxer Ee, Csaba Földy, Aoto J, Schwartz S, Jaoon Y.H. Kim, David Lukacsovich, and Kennedy Mj
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0303 health sciences ,Interneuron ,biology ,Subiculum ,Hippocampal formation ,Inhibitory postsynaptic potential ,Synapse ,03 medical and health sciences ,Electrophysiology ,0302 clinical medicine ,medicine.anatomical_structure ,medicine ,biology.protein ,GABAergic ,Neuroscience ,030217 neurology & neurosurgery ,Parvalbumin ,030304 developmental biology - Abstract
Ventral subiculum (vSUB) is integral to the regulation of stress and reward, however the intrinsic connectivity and synaptic properties of the inhibitory local circuit are poorly understood. Neurexin-3 (Nrxn3) is highly expressed in hippocampal inhibitory neurons, but its function at inhibitory synapses has remained elusive. Using slice electrophysiology, imaging, and single-cell RNA sequencing, we identify multiple roles for Nrxn3 at GABAergic parvalbumin (PV) interneuron synapses made onto vSUB regular spiking (RS) and burst spiking (BS) principal neurons. Surprisingly, we found that intrinsic connectivity and synaptic function of Nrxn3 in vSUB are sexually dimorphic. We reveal that vSUB PVs make preferential contact with RS neurons in males, but BS neurons in females. Furthermore, we determined that despite comparable Nrxn3 isoform expression in male and female PV neurons, Nrxn3 maintains synapse density at PV-RS synapses in males, but suppresses presynaptic release at the same synapses in females.HighlightsOverall inhibitory strength in ventral subiculum is cell-type specificPV circuits in ventral subiculum are organized sex-specificallyNrxn3 function in PV interneurons depends on postsynaptic cell identityNrxn3 has distinct functions at PV-RS synapses in females compared to malesAbstract FigureGraphical Abstract
- Published
- 2021
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