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

Jan M. Schulz, Frederic Knoflach, Maria-Clemencia Hernandez and Josef Bischofberger ()
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Jan M. Schulz: University of Basel
Frederic Knoflach: F. Hoffmann-La Roche Ltd
Maria-Clemencia Hernandez: F. Hoffmann-La Roche Ltd
Josef Bischofberger: University of Basel

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06004-8

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