| First Author | Schulz JM | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 3576 |
| PubMed ID | 30177704 | Mgi Jnum | J:267792 |
| Mgi Id | MGI:6267921 | Doi | 10.1038/s41467-018-06004-8 |
| Citation | Schulz JM, et al. (2018) Dendrite-targeting interneurons control synaptic NMDA-receptor activation via nonlinear alpha5-GABAA receptors. Nat Commun 9(1):3576 |
| abstractText | 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 alpha5-subunit- containing GABAA receptors (alpha5-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, alpha5-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 alpha5-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. |
