A critical role for α4βδ GABAA receptors in shaping learning deficits at puberty in mice

Hui Shen, Nicole Sabaliauskas, Ang Sherpa, André A. Fenton, Armin Stelzer, Chiye Aoki, Sheryl S. Smith

Research output: Contribution to journalArticle

Abstract

The onset of puberty defines a developmental stage when some learning processes are diminished, but the mechanism for this deficit remains unknown. We found that, at puberty, expression of inhibitory α4βδ γ-aminobutyric acid type A (GABAA) receptors (GABAR) increases perisynaptic to excitatory synapses in CA1 hippocampus. Shunting inhibition via these receptors reduced N-methyl-D-aspartate receptor activation, impairing induction of long-term potentiation (LTP). Pubertal mice also failed to learn a hippocampal, LTP-dependent spatial task that was easily acquired by δ-/- mice. However, the stress steroid THP (3αOH-5α[β]-pregnan-20- one), which reduces tonic inhibition at puberty, facilitated learning. Thus, the emergence of α4βδ GABARs at puberty impairs learning, an effect that can be reversed by a stress steroid.

Original languageEnglish (US)
Pages (from-to)1515-1518
Number of pages4
JournalScience
Volume327
Issue number5972
DOIs
StatePublished - Mar 19 2010

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