Neurexin-3 defines synapse- and sex-dependent diversity of GABAergic inhibition in ventral subiculum.
Neurexin-3 defines synapse- and sex-dependent diversity of GABAergic inhibition in ventral subiculum.
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DOI：
10.1016/j.celrep.2021.110098
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发表时间：
2021-12-07
期刊：
影响因子：
8.8
通讯作者：
Aoto J
中科院分区：
文献类型：
--
作者：
Boxer EE;Seng C;Lukacsovich D;Kim J;Schwartz S;Kennedy MJ;Földy C;Aoto J
腹侧亚核(VSUB)对应激和奖赏的调节是不可或缺的；然而，抑制性局部回路的内在连通性和突触特性却知之甚少。Neuresin-3(NRXN3)在海马区抑制性神经元中高表达，但其在抑制性突触中的作用尚不清楚。利用切片电生理学、成像和单细胞RNA测序，我们确定了NRXN3在vSUB规则峰(RS)和爆发峰(BS)主神经元上的GABA能小白蛋白(PV)神经元突触中的多重作用。令人惊讶的是，我们发现vSUB的内在连接性和vSUB中NRXN3的突触功能是性别二态的。我们发现，PVs优先接触雄性小鼠的RS神经元，而雌性小鼠的BS神经元。此外，我们确定，尽管NRXN3在雄性和雌性PV神经元中表达相似，但NRXN3基因敲除降低了雄性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，但增强了雌性PV-RS突触前释放和IPSC幅度。虽然神经尿毒素在海马区兴奋性突触中的不同作用正变得越来越清楚，但它在海马区抑制性突触中的作用却鲜为人知。Boxer等人。揭示在小白蛋白抑制性突触，在腹侧下丘脑环内，neuresin-3的功能和局部回路连接是细胞类型和性别特异性的。
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. While the diverse role of neurexins at hippocampal excitatory synapses is becoming more clear, the function of neurexins at hippocampal inhibitory synapses is less well known. Boxer et al. reveal that at parvalbumin inhibitory synapses, neurexin-3 function and local circuit connectivity are cell-type- and sex-specific within the ventral subiculum circuit.
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