MeCP2 Deficiency Alters the Response Selectivity of Prefrontal Cortical Neurons to Different Social Stimuli

Natalie Boyle, Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037.
Yipeng Li, Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037.
Xiaoqian Sun, Department of Computer Science, School of Engineering and Applied Science, The George Washington University, Washington, DC 20037.
Pan Xu, Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037.
Chien-Hsien Lai, Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037.
Sarah Betts, Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037.
Dian Guo, Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037.
Rahul Simha, Department of Computer Science, School of Engineering and Applied Science, The George Washington University, Washington, DC 20037.
Chen Zeng, Department of Physics, Columbia College of Art and Sciences, The George Washington University, Washington, DC 20037.
Jianyang Du, Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163 jdu15@uthsc.edu huilu@email.gwu.edu.
Hui Lu, Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037 jdu15@uthsc.edu huilu@email.gwu.edu.

Document Type

Journal Article

Publication Date

9-1-2024

Journal

eNeuro

Volume

11

Issue

9

DOI

10.1523/ENEURO.0003-24.2024

Keywords

MeCP2; in vivo calcium imaging; prefrontal cortex; prelimbic circuit; social discrimination; stimulus classification

Abstract

Rett syndrome (RTT), a severe neurodevelopmental disorder caused by mutations in the MeCP2 gene, is characterized by cognitive and social deficits. Previous studies have noted hypoactivity in the medial prefrontal cortex (mPFC) pyramidal neurons of MeCP2-deficient mice (RTT mice) in response to both social and nonsocial stimuli. To further understand the neural mechanisms behind the social deficits of RTT mice, we monitored excitatory pyramidal neurons in the prelimbic region of the mPFC during social interactions in mice. These neurons' activity was closely linked to social preference, especially in wild-type mice. However, RTT mice showed reduced social interest and corresponding hypoactivity in these neurons, indicating that impaired mPFC activity contributes to their social deficits. We identified six mPFC neural ensembles selectively tuned to various stimuli, with RTT mice recruiting fewer neurons to ensembles responsive to social interactions and consistently showing lower stimulus-ON ensemble transient rates. Despite these lower rates, RTT mice exhibited an increase in the percentage of social-ON neurons in later sessions, suggesting a compensatory mechanism for the decreased firing rate. This highlights the limited plasticity in the mPFC caused by MeCP2 deficiency and offers insights into the neural dynamics of social encoding. The presence of multifunctional neurons and those specifically responsive to social or object stimuli in the mPFC emphasizes its crucial role in complex behaviors and cognitive functions, with selective neuron engagement suggesting efficiency in neural activation that optimizes responses to environmental stimuli.

Department

Pharmacology and Physiology

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