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A critical role for alpha4betadelta GABAA receptors in shaping learning deficits at puberty in mice.

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 alpha4betadelta gamma-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 delta-/- mice. However, the stress steroid THP (3alphaOH-5alpha[beta]-pregnan-20-one), which reduces tonic inhibition at puberty, facilitated learning. Thus, the emergence of alpha4betadelta GABARs at puberty impairs learning, an effect that can be reversed by a stress steroid.

SUBMITTER: Shen H

PROVIDER: S-EPMC2887350 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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A critical role for alpha4betadelta GABAA receptors in shaping learning deficits at puberty in mice.

Shen Hui H Sabaliauskas Nicole N Sherpa Ang A Fenton André A AA Stelzer Armin A Aoki Chiye C Smith Sheryl S SS

Science (New York, N.Y.) 20100301 5972

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 alpha4betadelta gamma-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 ...[more]

PMID: 20299596

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