Loss of Calretinin in L5a impairs the formation of the barrel cortex leading to abnormal whisker-mediated behaviors

Mingzhao Su,Mengjie Yang,Baocong Yu,Kaixing Zhou,Congli Sun,Junhua Liu,Chunjie Zhao

doi:10.1186/s13041-021-00775-w

Abstract

The rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. Layer 5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of layer 5a in the development of the barrel cortex remains unclear. Previously, we found that calretinin is dynamically expressed in layer 5a. In this study, we analyzed calretinin KO mice and found that the dendritic complexity and length of layer 5a pyramidal neurons were significantly decreased after calretinin ablation. The membrane excitability and excitatory synaptic transmission of layer 5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, layer 4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Calretinin KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of layer 5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.

Highlights

Rodents use their whiskers to explore the presence and location of objects when moving through a nocturnal environment and evolved a whisker-barrel cortex system [1,2,3,4,5]
By analyzing calretinin knockout (Cr KO) mice, we found that loss of Cr results in a reduced complexity of layer 5a (L5a) pyramidal neuron dendrites, which leads to abnormal formation of the barrel wall and subsequently impairs the barrel and septa microcircuits
We analyzed the dendritic morphology of RFP+ neurons at P20 and found that control mice exhibited a typical morphology of L5a pyramidal neurons with an apical dendrite extending to layer 1 (L1) and several basal dendrites stretching to the sides and deeper [20]; the complexity of basal dendrites was significantly reduced in Cr KO mice (Fig. 1d)

Summary

Introduction

Rodents use their whiskers to explore the presence and location of objects when moving through a nocturnal environment and evolved a whisker-barrel cortex system [1,2,3,4,5]. As the information-receiving region, the barrel cortex plays a crucial role in integrating information resources and coordinating the movement of the whiskers and determines the function of the entire system [2, 6,7,8,9]. The barrel cortex consists of barrel and septa columns that receive various input signals through distinct pathways. As the main target of the paralemniscal pathway, layer 5a (L5a) is involved in both barrel and septa circuits and is considered to be an important component of information integration for the lemniscal and paralemniscal pathways [10, 15,16,17]. L5a pyramidal neurons directly accept the information inputs from the paralemniscal pathway and indirectly accept the information inputs from the lemniscal pathway. It has been observed that dendrites of L5a pyramidal neurons have a larger span and can establish synaptic

Methods

Results

Conclusion