University of Colorado Anschutz, Department of Pharmacology, Aurora, CO 80045, USA; Neuroscience Graduate Program, University of Colorado Anschutz, Aurora, CO 80045, USA.
Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland.
Cell Rep. 2021 Dec 7;37(10):110098. doi: 10.1016/j.celrep.2021.110098.
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 find that intrinsic connectivity of vSUB and synaptic function of Nrxn3 in vSUB are sexually dimorphic. We reveal that PVs make preferential contact with RS neurons in male mice, but BS neurons in female mice. Furthermore, we determine that despite comparable Nrxn3 isoform expression in male and female PV neurons, Nrxn3 knockout impairs synapse density, postsynaptic strength, and inhibitory postsynaptic current (IPSC) amplitude at PV-RS synapses in males, but enhances presynaptic release and IPSC amplitude in females.
腹侧下托（vSUB）是调节应激和奖励的重要组成部分；然而，抑制性局部回路的内在连接和突触特性仍不清楚。神经连接蛋白 3（Nrxn3）在海马抑制性神经元中高度表达，但它在抑制性突触中的功能仍然难以捉摸。使用切片电生理学、成像和单细胞 RNA 测序，我们确定了 Nrxn3 在 GABA 能神经元 parvalbumin（PV）中间神经元突触上的多个作用，这些突触与 vSUB 中的规则放电（RS）和爆发放电（BS）主神经元形成。令人惊讶的是，我们发现 vSUB 的内在连接和 Nrxn3 在 vSUB 中的突触功能存在性别二态性。我们发现，在雄性小鼠中，PV 优先与 RS 神经元形成接触，而在雌性小鼠中则与 BS 神经元形成接触。此外，我们确定尽管雄性和雌性 PV 神经元中 Nrxn3 同工型表达相当，但 Nrxn3 敲除会损害雄性 PV-RS 突触的突触密度、突触后强度和抑制性突触后电流（IPSC）幅度，但会增强雌性的突触前释放和 IPSC 幅度。
