Interneuron- and GABA(A) receptor-specific inhibitory synaptic plasticity in cerebellar Purkinje cells

Nat Commun. 2015 Jul 16:6:7364. doi: 10.1038/ncomms8364.

Abstract

Inhibitory synaptic plasticity is important for shaping both neuronal excitability and network activity. Here we investigate the input and GABA(A) receptor subunit specificity of inhibitory synaptic plasticity by studying cerebellar interneuron-Purkinje cell (PC) synapses. Depolarizing PCs initiated a long-lasting increase in GABA-mediated synaptic currents. By stimulating individual interneurons, this plasticity was observed at somatodendritic basket cell synapses, but not at distal dendritic stellate cell synapses. Basket cell synapses predominantly express β2-subunit-containing GABA(A) receptors; deletion of the β2-subunit ablates this plasticity, demonstrating its reliance on GABA(A) receptor subunit composition. The increase in synaptic currents is dependent upon an increase in newly synthesized cell surface synaptic GABA(A) receptors and is abolished by preventing CaMKII phosphorylation of GABA(A) receptors. Our results reveal a novel GABA(A) receptor subunit- and input-specific form of inhibitory synaptic plasticity that regulates the temporal firing pattern of the principal output cells of the cerebellum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cerebellum / metabolism*
  • Interneurons / metabolism*
  • Long-Term Potentiation
  • Mice
  • Mice, Knockout
  • Neural Inhibition*
  • Neuronal Plasticity*
  • Patch-Clamp Techniques
  • Phosphorylation
  • Purkinje Cells / metabolism*
  • Receptors, GABA / genetics*
  • Receptors, GABA / metabolism
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism

Substances

  • Gabrb2 protein, mouse
  • Receptors, GABA
  • Receptors, GABA-A
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium