Aberrantly integrated adult-born immature neurons disrupt brain-wide networks during spatial memory processing

Memory deficits observed in various neurological and psychiatric disorders may, in part, arise from dysregulated adult-born immature neurons (ABNs) in the dentate gyrus (DG). However, the mechanisms by which these aberrant neurons contribute to brain-wide network dysfunction and memory impairment remain poorly understood. Using a well-established mouse model with aberrantly integrated ABNs and associated memory deficits, we employed resting-state functional magnetic resonance imaging (rs-fMRI) and found that a few hundred dysregulated ABNs (<0.1% of total DG granule neurons) were sufficient to disrupt functional connectivity between the DG and the insular cortex, two regions lacking direct anatomical connections. Further investigation using rabies-based retrograde tracing and fiber photometry recording revealed that dysregulated ABNs impaired calcium dynamics, inter-regional synchrony, and temporal coordination across both local hippocampal circuits and distal regions, including the mediodorsal thalamus and insular cortex, during a spatial memory task. Together, these findings reveal how a small population of aberrantly integrated ABNs can disrupt brain-wide network dynamics and ultimately impair spatial memory processing.

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Publication Details

Journal
Molecular Psychiatry
Published
2025-11-22
DOI
https://doi.org/10.1038/s41380-025-03362-w
Primary Topic
Functional Brain Connectivity Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Aberrantly integrated adult-born immature neurons disrupt brain-wide networks during spatial memory processing

Hechen Bao, Yuguo Yu, Ian R. Wickersham, Ze-Ka Chen et al.
Molecular Psychiatry
Functional Brain Connectivity Studies
article

Aberrantly integrated adult-born immature neurons disrupt brain-wide networks during spatial memory processing

Hechen Bao, Yuguo Yu, Ian R. Wickersham, Ze-Ka Chen, Yan‐Jia Luo, Juan Song, Heather A. Sullivan, Yen‐Yu Ian Shih, Tzu-Hao Harry Chao, Zhiqiang Hu, Libo Zhang, Yadong Li, Sung‐Ho Lee
article en

Abstract

Memory deficits observed in various neurological and psychiatric disorders may, in part, arise from dysregulated adult-born immature neurons (ABNs) in the dentate gyrus (DG). However, the mechanisms by which these aberrant neurons contribute to brain-wide network dysfunction and memory impairment remain poorly understood. Using a well-established mouse model with aberrantly integrated ABNs and associated memory deficits, we employed resting-state functional magnetic resonance imaging (rs-fMRI) and found that a few hundred dysregulated ABNs (<0.1% of total DG granule neurons) were sufficient to disrupt functional connectivity between the DG and the insular cortex, two regions lacking direct anatomical connections. Further investigation using rabies-based retrograde tracing and fiber photometry recording revealed that dysregulated ABNs impaired calcium dynamics, inter-regional synchrony, and temporal coordination across both local hippocampal circuits and distal regions, including the mediodorsal thalamus and insular cortex, during a spatial memory task. Together, these findings reveal how a small population of aberrantly integrated ABNs can disrupt brain-wide network dynamics and ultimately impair spatial memory processing.

Molecular PsychiatryVol. 31(4)
University of North Carolina at Chapel Hill (US), University of North Carolina Health Care (US), McGovern Institute for Brain Research (US), Fudan University (CN), Shanghai Institute for Science of Science (CN), Shanghai Center for Brain Science and Brain-Inspired Technology (CN), University of California, Berkeley (US)
University of Texas at San Antonio, Tata Consultancy Services, National Institutes of Health, National Cancer Institute, National Institute of Environmental Health Sciences
Openalex Percentile: Top 64%
Functional Brain Connectivity Studies
DOIOpen Access PDFOpenAlex
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