A new AAV tool for highly preferentially targeting hippocampal CA2

Siqi Peng; Wenzhen Gu; Wenxiu Zhu; Yan Zhuang; Xiuqi Yang; Yaochen Lv; Sibie Meng; Wei Xie; Moyi Li

doi:10.1186/s13041-023-01038-6

A new AAV tool for highly preferentially targeting hippocampal CA2

Mol Brain. 2023 Jun 11;16(1):50. doi: 10.1186/s13041-023-01038-6.

Authors

Siqi Peng¹, Wenzhen Gu¹, Wenxiu Zhu¹, Yan Zhuang¹, Xiuqi Yang¹, Yaochen Lv¹, Sibie Meng¹, Wei Xie^{1

2}, Moyi Li^{3

4}

Affiliations

¹ School of Life Science and Technology, The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, 210096, China.
² Jiangsu Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.
³ School of Life Science and Technology, The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, 210096, China. limoyi@seu.edu.cn.
⁴ Jiangsu Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China. limoyi@seu.edu.cn.

Abstract

Mice hippocampus contains three prominent subregions, CA1, CA3 and DG and is well regarded as an essential multiple task processor for learning, memory and cognition based on tremendous studies on these three subregions. The narrow region sandwiched between CA1 and CA3 called CA2 has been neglected for a long time. But it raises great attentions recently since this region manifests the indispensable role in social memory. Its unique physical position connecting CA1 and CA3 suggests the potential novel functions besides social memory regulation. But the CA2 is too small to be accurately targeted. A flexible AAV tool capable of accurately and efficiently targeting this region is highly demanded. To fill this gap, we generate an AAV expressing Cre driven by the mini Map3k15 promoter, AAV/M1-Cre, which can be easily utilized to help tracing and manipulating CA2 pyramidal neurons. However, M1-Cre labeled a small percentage of M1⁺RGS14^- neurons that do not colocalize with any RGS14⁺/STEP⁺/PEP4⁺/Amigo2⁺ pyramidal neurons. They are proved to be the mixture of normal CA2 pyramidal neurons, CA3-like neurons in CA2-CA3 mixed border, some CA2 interneurons and rarely few CA1-like neurons, which are probably the ones projecting to the revealed CA2 downstream targets, VMH, STHY and PMV in WT mice injecting this AAV/M1-Cre virus but not in Amigo2-Cre mice. Though it is still challenging to get a pure CA2 tracking and manipulation system, this tool provides a new, more flexible and extended strategy for in-depth CA2 functional study in the future.

Keywords: AAV tool; Cornu ammonis 2; Hippocampus; Neural activity regulation; Neural tracing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cognition
Hippocampus
Interneurons
Mice
Neurons*
Pyramidal Cells*