Center for Neural Science, New York University, New York, New York 10003.
Center for Neural Science, New York University, New York, New York 10003
J Neurosci. 2024 Jun 5;44(23):e0957232024. doi: 10.1523/JNEUROSCI.0957-23.2024.
Interneurons in the medial prefrontal cortex (PFC) regulate local neural activity to influence cognitive, motivated, and emotional behaviors. Parvalbumin-expressing (PV+) interneurons are the primary mediators of thalamus-evoked feed-forward inhibition across the mouse cortex, including the anterior cingulate cortex, where they are engaged by inputs from the mediodorsal (MD) thalamus. In contrast, in the adjacent prelimbic (PL) cortex, we find that PV+ interneurons are scarce in the principal thalamorecipient layer 3 (L3), suggesting distinct mechanisms of inhibition. To identify the interneurons that mediate MD-evoked inhibition in PL, we combine slice physiology, optogenetics, and intersectional genetic tools in mice of both sexes. We find interneurons expressing cholecystokinin (CCK+) are abundant in L3 of PL, with cells exhibiting fast-spiking (fs) or non-fast-spiking (nfs) properties. MD inputs make stronger connections onto fs-CCK+ interneurons, driving them to fire more readily than nearby L3 pyramidal cells and other interneurons. CCK+ interneurons in turn make inhibitory, perisomatic connections onto L3 pyramidal cells, where they exhibit cannabinoid 1 receptor (CB1R) mediated modulation. Moreover, MD-evoked feed-forward inhibition, but not direct excitation, is also sensitive to CB1R modulation. Our findings indicate that CCK+ interneurons contribute to MD-evoked inhibition in PL, revealing a mechanism by which cannabinoids can modulate MD-PFC communication.
前额叶皮层（PFC）中的中间神经元调节局部神经活动，从而影响认知、动机和情绪行为。表达 Parvalbumin（PV+）的中间神经元是丘脑诱发的前扣带皮层（ACC）中前馈抑制的主要介导者，包括前扣带皮层，它们由中背侧（MD）丘脑的输入激活。相比之下，在相邻的额前皮质（PL）皮质中，我们发现 PV+中间神经元在主要的丘脑接受层 3（L3）中很少，这表明存在不同的抑制机制。为了确定介导 MD 诱发的 PL 抑制的中间神经元，我们在雄性和雌性小鼠中结合了切片生理学、光遗传学和交叉遗传工具。我们发现，胆囊收缩素（CCK+）表达的中间神经元在 PL 的 L3 中丰富，具有快速放电（fs）或非快速放电（nfs）特性的细胞。MD 输入与 fs-CCK+中间神经元建立更强的连接，驱动它们比附近的 L3 锥体神经元和其他中间神经元更容易放电。反过来，CCK+中间神经元在 L3 锥体神经元上形成抑制性、体周连接，在那里它们表现出大麻素 1 型受体（CB1R）介导的调节。此外，MD 诱发的前馈抑制，而不是直接兴奋，也对 CB1R 调节敏感。我们的发现表明，CCK+中间神经元有助于 PL 中的 MD 诱发抑制，揭示了大麻素可以调节 MD-PFC 通讯的机制。
