Dendrite-targeting interneurons control synaptic NMDA-receptor activation via nonlinear α5-GABA A receptors

Nat Commun. 2018 Sep 3;9(1):3576. doi: 10.1038/s41467-018-06004-8.

Abstract

Dendrite-targeting GABAergic interneurons powerfully control postsynaptic integration, synaptic plasticity, and learning. However, the mechanisms underlying the efficient GABAergic control of dendritic electrogenesis are not well understood. Using subtype-selective blockers for GABAA receptors, we show that dendrite-targeting somatostatin interneurons and NO-synthase-positive neurogliaform cells preferentially activate α5-subunit- containing GABAA receptors (α5-GABAARs), generating slow inhibitory postsynaptic currents (IPSCs) in hippocampal CA1 pyramidal cells. By contrast, only negligible contribution of these receptors could be found in perisomatic IPSCs, generated by fast-spiking parvalbumin interneurons. Remarkably, α5-GABAAR-mediated IPSCs were strongly outward-rectifying generating 4-fold larger conductances above -50 mV than at rest. Experiments and modeling show that synaptic activation of these receptors can very effectively control voltage-dependent NMDA-receptor activation as well as Schaffer-collateral evoked burst firing in pyramidal cells. Taken together, nonlinear-rectifying α5-GABAARs with slow kinetics match functional NMDA-receptor properties and thereby mediate powerful control of dendritic postsynaptic integration and action potential firing by dendrite-targeting interneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • CA1 Region, Hippocampal / cytology
  • Dendrites / metabolism*
  • Inhibitory Postsynaptic Potentials*
  • Interneurons / metabolism*
  • Mice
  • Mice, Transgenic
  • Parvalbumins
  • Patch-Clamp Techniques
  • Pyramidal Cells / metabolism*
  • Receptors, GABA-A / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synapses / metabolism*
  • Synaptic Transmission

Substances

  • Gabra5 protein, mouse
  • Parvalbumins
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate