Alterations of Sensory-related Functional Brain Network Connectivity in Nrsn2 Homozygous Knockout Mice

Yuan Yi; Fei Dai; Yuwen Zhang; Jiawei Han; Jialu Wei; Lingbo Wang; He Wang; Yu An

doi:10.1007/s43657-024-00181-x

Alterations of Sensory-related Functional Brain Network Connectivity in Nrsn2 Homozygous Knockout Mice

Phenomics. 2024 Nov 18;4(5):473-486. doi: 10.1007/s43657-024-00181-x. eCollection 2024 Oct.

Authors

Yuan Yi^#¹, Fei Dai^#², Yuwen Zhang², Jiawei Han², Jialu Wei¹, Lingbo Wang³, He Wang^{2

4

5}, Yu An¹

Affiliations

¹ Human Phenome Institute, Institute of Medical Genetics and Genomics, MOE Key Laboratory of Contemporary Anthropology, Zhangjiang Fudan International Innovation Center, Fudan University, 825 Zhangheng Road, Shanghai, 201203 China.
² Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, 201203 China.
³ Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Institute of Reproduction and Development, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200433 China.
⁴ Human Phenome Institute, Fudan University, Shanghai, 201203 China.
⁵ Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, 200032 China.

^# Contributed equally.

PMID: 39723223
PMCID: PMC11666851 (available on 2025-10-01)
DOI: 10.1007/s43657-024-00181-x

Abstract

Neurensin-2 (Nrsn2) is a neuro-specific gene linked to neurodevelopmental disorders and has recently been reported to function as a bidirectional emotional regulator, highlighting its molecular roles in the nervous system. However, the connections between Nrsn2, brain architecture, and functionality remain to be fully elucidated. Our study utilized 11.7 T multimodal magnetic resonance imaging (MRI) to assess the impact of Nrsn2 gene knockout on the brain's microstructure, regional functional activity, and network connectivity during different developmental phases in mice. We observed significant changes in the functional brain network connectivity of Nrsn2 ^-/- mice without marked differences in brain microstructure or regional activity. These changes were particularly pronounced in sensory-related areas, such as the gustatory and auditory systems, in both juvenile and adult specimens. Previous studies have correlated the enhanced Default Mode Network (DMN) with depression, and Nrsn2 knockout has been associated with stress resilience. Our findings further revealed reduced connectivity in various DMN regions in adult Nrsn2 ^-/- mice, suggesting a potential link to increased stress tolerance. Moreover, the sensory system's critical role in environmental perception implies that alterations in network connectivity due to Nrsn2 knockout could affect the processing and integration of external inputs, thereby influencing emotional experiences.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00181-x.

Keywords: Gene editing; Magnetic resonance imaging; Network analysis; Neurensin-2; Neurodevelopmental disorders; Sensory system.

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