Open AccessDendrite-targeting interneurons control synaptic NMDA-receptor activation via nonlinear α5-GABAA receptors
Author(s) -
Jan M. Schulz,
Frédéric Knoflach,
Maria-Clemencia Hernández,
Josef Bischofberger
Publication year - 2018
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/s41467-018-06004-8
Subject(s) - neuroscience , postsynaptic potential , gabaa receptor , inhibitory postsynaptic potential , gabaergic , excitatory postsynaptic potential , postsynaptic current , parvalbumin , nmda receptor , dendrite (mathematics) , interneuron , hippocampal formation , apical dendrite , chemistry , receptor , biology , soma , biochemistry , geometry , mathematics
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 GABA A receptors, we show that dendrite-targeting somatostatin interneurons and NO-synthase-positive neurogliaform cells preferentially activate α5-subunit- containing GABA A receptors (α5-GABA A Rs), 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-GABA A R-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-GABA A Rs 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.