Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, TX, 78229, USA.
South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, TX, USA.
Nat Commun. 2023 Oct 20;14(1):6653. doi: 10.1038/s41467-023-42484-z.
People with schizophrenia show hyperactivity in the ventral hippocampus (vHipp) and we have previously demonstrated distinct behavioral roles for vHipp cell populations. Here, we test the hypothesis that parvalbumin (PV) and somatostatin (SST) interneurons differentially innervate and regulate hippocampal pyramidal neurons based on their projection target. First, we use eGRASP to show that PV-positive interneurons form a similar number of synaptic connections with pyramidal cells regardless of their projection target while SST-positive interneurons preferentially target nucleus accumbens (NAc) projections. To determine if these anatomical differences result in functional changes, we used in vivo opto-electrophysiology to show that SST cells also preferentially regulate the activity of NAc-projecting cells. These results suggest vHipp interneurons differentially regulate that vHipp neurons that project to the medial prefrontal cortex (mPFC) and NAc. Characterization of these cell populations may provide potential molecular targets for the treatment schizophrenia and other psychiatric disorders associated with vHipp dysfunction.
精神分裂症患者的腹侧海马体（vHipp）表现出过度活跃，我们之前已经证明 vHipp 细胞群体具有不同的行为作用。在这里，我们假设基于其投射目标，囊泡相关蛋白（PV）和生长抑素（SST）中间神经元会以不同的方式支配和调节海马锥体神经元。首先，我们使用 eGRASP 表明，无论其投射目标如何，PV 阳性中间神经元与锥体细胞形成相似数量的突触连接，而 SST 阳性中间神经元优先靶向伏隔核（NAc）投射。为了确定这些解剖差异是否导致功能变化，我们使用体内光电器生理学表明 SST 细胞也优先调节 NAc 投射细胞的活性。这些结果表明 vHipp 中间神经元以不同的方式调节投射到内侧前额叶皮层（mPFC）和 NAc 的 vHipp 神经元。这些细胞群体的特征可能为治疗精神分裂症和其他与 vHipp 功能障碍相关的精神疾病提供潜在的分子靶点。
