Input-Specific NMDAR-Dependent Potentiation of Dendritic GABAergic Inhibition

Neuron. 2018 Jan 17;97(2):368-377.e3. doi: 10.1016/j.neuron.2017.12.032.

Abstract

Preservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors leads to input-specific long-term potentiation of dendritic inhibition mediated by somatostatin-expressing interneurons. This form of plasticity is expressed postsynaptically and requires both CaMKIIα and the β2 subunit of the GABA-A receptor. Importantly, this process may function to preserve dendritic inhibition, as genetic deletion of NMDAR signaling results in a selective weakening of dendritic inhibition. Overall, our results reveal a new mechanism for linking excitatory and inhibitory input in neuronal dendrites and provide novel insight into the homeostatic regulation of synaptic transmission in cortical circuits.

Keywords: CaMKIIα; GABA; homeostatic; interneuron; optogenetic; parvalbumin; plasticity; somatostatin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling / physiology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / physiology
  • Dendrites / physiology*
  • Female
  • Long-Term Potentiation / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / physiology*
  • Neural Inhibition / physiology*
  • Pyramidal Cells / physiology
  • Receptors, GABA-A / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • gamma-Aminobutyric Acid / physiology*

Substances

  • Nerve Tissue Proteins
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • gamma-Aminobutyric Acid
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2