Whole-Brain Mapping the Direct Inputs of Dorsal and Ventral CA1 Projection Neurons.

Sijue Tao,Xuefeng Yu,Yang Zhao,Qing Liu,Yihang Wang,Fuqiang Xu,Jundan Peng,Xiaobin He,Sen Jin

doi:10.3389/fncir.2021.643230

Abstract

The CA1, an important subregion of the hippocampus, is anatomically and functionally heterogeneous in the dorsal and ventral hippocampus. Here, to dissect the distinctions between the dorsal (dCA1) and ventral CA1 (vCA1) in anatomical connections, we systematically analyzed the direct inputs to dCA1 and vCA1 projection neurons (PNs) with the rabies virus-mediated retrograde trans-monosynaptic tracing system in Thy1-Cre mice. Our mapping results revealed that the input proportions and distributions of dCA1 and vCA1 PNs varied significantly. Inside the hippocampal region, dCA1 and vCA1 PNs shared the same upstream brain regions, but with distinctive distribution patterns along the rostrocaudal axis. The intrahippocampal inputs to the dCA1 and vCA1 exhibited opposite trends, decreasing and increasing gradually along the dorsoventral axis, respectively. For extrahippocampal inputs, dCA1 and vCA1 shared some monosynaptic projections from certain regions such as pallidum, striatum, hypothalamus, and thalamus. However, vCA1, not dCA1, received innervations from the subregions of olfactory areas and amygdala nuclei. Characterization of the direct input networks of dCA1 and vCA1 PNs may provide a structural basis to understand the differential functions of dCA1 and vCA1.

Highlights

IntroductionSince the dorsal and ventral hippocampi are proposed to participate in different functions (Amaral and Witter, 1989; Moser et al, 1995), evidence on the anatomical and functional segregations along the dorsoventral axis ( referred to as the longitudinal or septotemporal axis) has been cumulated (Dong et al, 2009; Fanselow and Dong, 2010; Bannerman et al, 2014; Strange et al, 2014)
Since there was no significant difference in convergence index (P = 0.317) between the two experiment groups, the differences in the monosynaptic afferents represent the differences in the connection strength between the CA1 projection neurons (PNs) and their upstream neurons
Our analysis demonstrated that contralateral CA1 made almost no interhemispheric/contralateral connections to ventral CA1 (vCA1) PNs (Figures 4A,B)

Summary

Introduction

Since the dorsal and ventral hippocampi are proposed to participate in different functions (Amaral and Witter, 1989; Moser et al, 1995), evidence on the anatomical and functional segregations along the dorsoventral axis ( referred to as the longitudinal or septotemporal axis) has been cumulated (Dong et al, 2009; Fanselow and Dong, 2010; Bannerman et al, 2014; Strange et al, 2014). Literature has shown that dCA1 processes information involved in spatial location and memory (Hunsaker et al, 2008; Fanselow and Dong, 2010), while the vCA1 modulates mood-related behavior like stress and anxiety (Jacobson and Sapolsky, 1991; Parfitt et al, 2017; Jimenez et al, 2018; Padilla-Coreano et al, 2019). Distinctive heterogeneities between dCA1 and vCA1 were found in dendritic morphology, synaptic physiology, intrinsic excitability, and gene expressions (Leonardo et al, 2006; Dougherty et al, 2012, 2013; Malik et al, 2016; Malik and Johnston, 2017; Evans and Dougherty, 2018; Dougherty, 2020)

Methods

Results

Discussion

Conclusion