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Astrocytic Gap Junctions Contribute to Aberrant Neuronal Synchronization in a Mouse Model of MeCP2 Duplication
Shengnan Xia1,2, Hua-Tai Xu3,4
1Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.
Neuroscience Bulletin
|February 11, 2022
Summary
Autism risk gene MeCP2 duplication in young mice causes abnormal brain synchrony, driven by astrocyte networks. This effect diminishes with age, suggesting a critical developmental window.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Abnormal neuronal synchrony is observed in autism spectrum disorder (ASD) patients.
- The precise neural mechanisms underlying this synchrony, particularly concerning genetic factors like MeCP2, remain largely unknown.
Purpose of the Study:
- To investigate the role of the human autism risk gene MeCP2 in regulating neuronal and astrocytic synchrony during development.
- To elucidate the contribution of astrocyte networks to abnormal brain activity in a mouse model of MeCP2 duplication syndrome.
Main Methods:
- In vivo two-photon imaging and whole-cell recording in transgenic (Tg1) mice over-expressing MeCP2 and wild-type littermates.
- Analysis of neuronal and astrocytic activity, including slow inward currents (SICs) and gap junction coupling.
- Pharmacological manipulation of astrocytic gap junctions.
Main Results:
- Young Tg1 mice exhibited significantly higher neuronal synchrony compared to wild-type, linked to prevalent giant slow inward currents (SICs).
- Astrocytes in young Tg1 mice showed increased dynamic activity and synchrony.
- Blocking astrocytic gap junctions reduced SICs and overall neuronal synchrony in Tg1 mice, without altering Cx43 expression or coupling efficiency.
Conclusions:
- Astrocytic gap junctions facilitate, but do not directly trigger, abnormal neuronal synchrony in young MeCP2 duplication mice.
- The astrocyte network plays a crucial role in the pathogenesis of MeCP2 duplication syndrome, highlighting potential therapeutic targets.
