Tactile modulation of memory and anxiety requires dentate granule cells along the dorsoventral axis

Chi Wang,Ji Hu,Yi-Jun Liu,Hui Liu,Xing-Xing Wang,Ping Fang,Chen Wu,Jing-Ying Yu,Kun Li,Zhen-Zhen Wu,Hao Wang,Shu-Min Duan,Mathias V Schmidt,Qian Gong,Yan Gu,Bing-Xing Pan,Xiao-Dong Wang

doi:10.1038/s41467-020-19874-8

Abstract

Touch can positively influence cognition and emotion, but the underlying mechanisms remain unclear. Here, we report that tactile experience enrichment improves memory and alleviates anxiety by remodeling neurons along the dorsoventral axis of the dentate gyrus (DG) in adult mice. Tactile enrichment induces differential activation and structural modification of neurons in the dorsal and ventral DG, and increases the presynaptic input from the lateral entorhinal cortex (LEC), which is reciprocally connected with the primary somatosensory cortex (S1), to tactile experience-activated DG neurons. Chemogenetic activation of tactile experience-tagged dorsal and ventral DG neurons enhances memory and reduces anxiety respectively, whereas inactivation of these neurons or S1-innervated LEC neurons abolishes the beneficial effects of tactile enrichment. Moreover, adulthood tactile enrichment attenuates early-life stress-induced memory deficits and anxiety-related behavior. Our findings demonstrate that enriched tactile experience retunes the pathway from S1 to DG and enhances DG neuronal plasticity to modulate cognition and emotion.

Highlights

Touch can positively influence cognition and emotion, but the underlying mechanisms remain unclear
Since memory and anxiety are differentially modulated by dentate gyrus (DG) neurons along the hippocampal dorsoventral axis[25,26], it is possible that tactile inputs converge on the DG via the lateral entorhinal cortex (LEC) to shape cognitive and emotional processes
A comparison of different enrichment conditions revealed that tactile enrichment mainly increased mushroom spine density, while multimodal enrichment markedly increased thin and total spine density in DG neurons (Supplementary Fig. 7b–i). These results indicate that tactile enrichment evokes differential dendritic spine remodeling in dorsal DG (dDG) and ventral DG (vDG) granule cells

Summary

Introduction

Touch can positively influence cognition and emotion, but the underlying mechanisms remain unclear. Tactile enrichment induces differential activation and structural modification of neurons in the dorsal and ventral DG, and increases the presynaptic input from the lateral entorhinal cortex (LEC), which is reciprocally connected with the primary somatosensory cortex (S1), to tactile experience-activated DG neurons. Chemogenetic activation of tactile experiencetagged dorsal and ventral DG neurons enhances memory and reduces anxiety respectively, whereas inactivation of these neurons or S1-innervated LEC neurons abolishes the beneficial effects of tactile enrichment. Since memory and anxiety are differentially modulated by DG neurons along the hippocampal dorsoventral axis[25,26], it is possible that tactile inputs converge on the DG via the LEC to shape cognitive and emotional processes. Our results show that recurrent tactile enrichment enhanced synaptic plasticity in dDG and vDG granule cells to improve memory and reduce anxiety, respectively, and attenuated early life stress-induced behavioral and structural abnormalities

Methods

Results

Conclusion