Altered synaptic transmission and maturation of hippocampal CA1 neurons in a mouse model of human chr16p11.2 microdeletion

Lu, H. C., Mills, A. A., Tian, D. (March 2018) Altered synaptic transmission and maturation of hippocampal CA1 neurons in a mouse model of human chr16p11.2 microdeletion. J Neurophysiol, 119 (3). pp. 1005-1018. ISSN 0022-3077

URL: https://www.ncbi.nlm.nih.gov/pubmed/29212915
DOI: 10.1152/jn.00306.2017

Abstract

The pathophysiology of neurodevelopmental disorders is often expressed early in infancy and toddlerhood. Mouse models of syndromic disorders have provided insight regarding mechanisms of action, but most studies have focused on characterization in juveniles and adults. Insight into developmental trajectories, particularly related to circuit and synaptic function, likely will yield important information regarding disorder pathogenesis that leads to symptom progression. Chromosome 16p11.2 microdeletion is one of the most common copy number variations associated with a spectrum of neurodevelopmental disorders. Yet, how haploinsufficiency of chr16p11.2 affects early synaptic maturation and function is unknown. To address this knowledge gap, the present study focused on three key components of circuit formation and function-basal synaptic transmission, local circuit function, and maturation of glutamatergic synapses -in developing hippocampal CA1 neurons in a chr16p11.2 microdeletion mouse model. The data demonstrate increased excitability, imbalance in excitation and inhibition, and accelerated maturation of glutamatergic synapses in heterozygous mutant CA1 neurons. Given the critical role of early synaptic development in shaping neuronal connectivity and circuitry formation, these newly identified synaptic abnormalities in chr16p11.2 microdeletion mice may alter the developmental trajectory and function of the developing brain.

Item Type: Paper
Uncontrolled Keywords: chr16p11.2 microdeletion excitation/inhibition glutamatergic synapse hippocampus CA1 silent synapse
Subjects: organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > synaptic transmission
CSHL Authors:
Communities: CSHL labs > Mills lab
Depositing User: Matt Covey
Date: 1 March 2018
Date Deposited: 14 Dec 2017 17:26
Last Modified: 26 Mar 2018 19:40
Related URLs:
URI: http://repository.cshl.edu/id/eprint/35719

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