Correlation Analysis of Molecularly-Defined Cortical Interneuron Populations with Morpho-Electric Properties in Layer V of Mouse Neocortex

 Jun‑Wei Cao1  · Xiao‑Yi Mao2  · Liang Zhu3  · Zhi‑Shuo Zhou4  · Shao‑Na Jiang1  · Lin‑Yun Liu1  · Shu‑Qing Zhang1  · Yinghui Fu1  · Wen‑Dong Xu5  · Yong‑Chun Yu1
1 Jing’an District Central Hospital of Shanghai, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China 
2 School of Life Sciences, Fudan University, Shanghai 200433, China 
3 Department of Vascular Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China 
4 School of Data Science, Fudan University, Shanghai 200433, China 
5 The National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200032, China

Abstract
Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.

Keywords
Cortical interneuron; Cell population; Transcriptomic signature; Morpho-electrical properties; Correlation analysis; Brain area