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

  • Shen H
  • Sabaliauskas N
  • Sherpa A
 et al. 
  • 76

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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.

Author-supplied keywords

  • Animals
  • CA1 Region, Hippocampal
  • CA1 Region, Hippocampal: cytology
  • CA1 Region, Hippocampal: metabolism
  • Dendrites
  • Dendritic Spines
  • Dendritic Spines: metabolism
  • Excitatory Postsynaptic Potentials
  • Female
  • GABA-A Receptor Antagonists
  • Learning
  • Learning: drug effects
  • Long-Term Potentiation
  • Mice
  • Mice, Inbred C57BL
  • N-Methylaspartate
  • N-Methylaspartate: metabolism
  • Neural Inhibition
  • Patch-Clamp Techniques
  • Pregnanolone
  • Pregnanolone: pharmacology
  • Pyramidal Cells
  • Pyramidal Cells: metabolism
  • Receptors, GABA-A
  • Receptors, GABA-A: metabolism
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, N-Methyl-D-Aspartate: metabolism
  • Sexual Maturation
  • Spatial Behavior

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Authors

  • Hui Shen

  • Nicole Sabaliauskas

  • Ang Sherpa

  • André A Fenton

  • Armin Stelzer

  • Chiye Aoki

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