TY - JOUR
T1 - A critical role for α4βδ GABAA receptors in shaping learning deficits at puberty in mice
AU - Shen, Hui
AU - Sabaliauskas, Nicole
AU - Sherpa, Ang
AU - Fenton, André A.
AU - Stelzer, Armin
AU - Aoki, Chiye
AU - Smith, Sheryl S.
PY - 2010/3/19
Y1 - 2010/3/19
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1184245
DO - 10.1126/science.1184245
M3 - Article
C2 - 20299596
AN - SCOPUS:77949779421
SN - 0036-8075
VL - 327
SP - 1515
EP - 1518
JO - Science
JF - Science
IS - 5972
ER -