Center for Neural Science, New York University, New York, United States.
Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Boston, United States.
Elife. 2020 Oct 9;9:e55267. doi: 10.7554/eLife.55267.
Connections from the ventral hippocampus (vHPC) to the prefrontal cortex (PFC) regulate cognition, emotion, and memory. These functions are also tightly controlled by inhibitory networks in the PFC, whose disruption is thought to contribute to mental health disorders. However, relatively little is known about how the vHPC engages different populations of interneurons in the PFC. Here we use slice physiology and optogenetics to study vHPC-evoked feed-forward inhibition in the mouse PFC. We first show that cholecystokinin (CCK+), parvalbumin (PV+), and somatostatin (SOM+) expressing interneurons are prominent in layer 5 (L5) of infralimbic PFC. We then show that vHPC inputs primarily activate CCK+ and PV+ interneurons, with weaker connections onto SOM+ interneurons. CCK+ interneurons make stronger synapses onto pyramidal tract (PT) cells over nearby intratelencephalic (IT) cells. However, CCK+ inputs undergo depolarization-induced suppression of inhibition (DSI) and CB1 receptor modulation only at IT cells. Moreover, vHPC-evoked feed-forward inhibition undergoes DSI only at IT cells, confirming a central role for CCK+ interneurons. Together, our findings show how vHPC directly engages multiple populations of inhibitory cells in deep layers of the infralimbic PFC, highlighting unexpected roles for both CCK+ interneurons and endocannabinoid modulation in hippocampal-prefrontal communication.
腹侧海马体（vHPC）与前额叶皮层（PFC）的连接调节认知、情感和记忆。这些功能也受到 PFC 中抑制性网络的严格控制，其破坏被认为是导致心理健康障碍的原因之一。然而，人们对 vHPC 如何与 PFC 中的不同中间神经元群体相互作用知之甚少。在这里，我们使用切片生理学和光遗传学来研究小鼠 PFC 中的 vHPC 诱发的前馈抑制。我们首先表明，胆囊收缩素（CCK+）、囊泡蛋白（PV+）和生长抑素（SOM+）表达的中间神经元在扣带回前皮质的 L5 层中较为突出。然后我们表明，vHPC 输入主要激活 CCK+和 PV+中间神经元，对 SOM+中间神经元的连接较弱。CCK+中间神经元在附近的内脑（IT）细胞上与锥体束（PT）细胞形成更强的突触。然而，只有在 IT 细胞上，CCK+输入才会经历去极化诱导的抑制（DSI）和 CB1 受体调节。此外，vHPC 诱发的前馈抑制仅在 IT 细胞上发生 DSI，证实了 CCK+中间神经元的核心作用。总之，我们的研究结果表明 vHPC 如何直接与扣带回前皮质深层的多种抑制性细胞相互作用，突出了 CCK+中间神经元和内源性大麻素调节在海马-前额叶通讯中的意想不到的作用。
