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Science 327 (5972): 1515-1518

Copyright © 2010 by the American Association for the Advancement of Science

A Critical Role for {alpha}{delta} GABAA Receptors in Shaping Learning Deficits at Puberty in Mice

Hui Shen,1,* Nicole Sabaliauskas,1,2,* Ang Sherpa,1,3 André A. Fenton,1,3,4 Armin Stelzer,1,3,4 Chiye Aoki,2 Sheryl S. Smith1,3,4,{dagger}

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 {alpha}{delta} {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 (3{alpha}OH-5{alpha}[β]-pregnan-20-one), which reduces tonic inhibition at puberty, facilitated learning. Thus, the emergence of {alpha}{delta} GABARs at puberty impairs learning, an effect that can be reversed by a stress steroid.

1 Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
2 Center for Neural Science, New York University, 4 Washington Place, New York, NY 10003, USA.
3 Program in Neural and Behavioral Science, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
4 The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: sheryl.smith{at}downstate.edu


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