Manipulation of α4βδ GABAA receptors alters synaptic pruning in layer 3 prelimbic prefrontal cortex and impairs temporal order recognition: Implications for schizophrenia and autism

•α4βδ GABAA receptors increase at puberty in layer 3 male prelimbic cortex.•Targeting these receptors with drugs or by knock-out alters spine pruning.•α4 knock-out increases spines and impairs temporal order memory.•An α4βδ agonist decreases spines and impairs temporal order memory.•These findings m...

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Bibliographic Details
Published in:Brain research 2024-07, Vol.1835, p.148929-148929, Article 148929
Main Authors: Smith, Sheryl S, Benanni, Safae, Jones, Quiana, Kenney, Lindsay, Evrard, Matthew R.
Format: Article
Language:English
Subjects:
Alpha4-beta-delta GABAA receptor
Autism spectrum disorder
Dendritic spine
Prelimbic prefrontal cortex
Schizophrenia
Temporal order memory
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Summary:•α4βδ GABAA receptors increase at puberty in layer 3 male prelimbic cortex.•Targeting these receptors with drugs or by knock-out alters spine pruning.•α4 knock-out increases spines and impairs temporal order memory.•An α4βδ agonist decreases spines and impairs temporal order memory.•These findings may be relevant for ASD and SCZ where spine density/recency memory are abnormal. Temporal order memory is impaired in autism spectrum disorder (ASD) and schizophrenia (SCZ). These disorders, more prevalent in males, result in abnormal dendritic spine pruning during adolescence in layer 3 (L3) medial prefrontal cortex (mPFC), yielding either too many (ASD) or too few (SCZ) spines. Here we tested whether altering spine density in neural circuits including the mPFC could be associated with impaired temporal order memory in male mice. We have shown that α4βδ GABAA receptors (GABARs) emerge at puberty on spines of L5 prelimbic mPFC (PL) where they trigger pruning. We show here that α4βδ receptors also increase at puberty in L3 PL (P 
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2024.148929