Abstract
Excitatory synaptic inputs arriving at the dendrites of a neuron can engage active mechanisms that nonlinearly amplify the depolarizing currents. This supralinear synaptic integration is subject to modulation by inhibition. However, the specific rules by which different subtypes of interneurons affect the modulation have remained largely elusive. To examine how inhibition influences active synaptic integration, we optogenetically manipulated the activity of two subtypes of interneurons: dendrite-targeting somatostatin-expressing (SST) interneurons and perisomatic-targeting parvalbumin-expressing (PV) interneurons. In acute slices of mouse primary visual cortex, electrical stimulation evoked nonlinear synaptic integration that depended on N-methyl-D-aspartate (NMDA) receptors. Optogenetic activation of SST interneurons in conjunction with electrical stimulation resulted in predominantly divisive inhibitory gain control, reducing the magnitude of the supralinear response without affecting its threshold. PV interneuron activation, on the other hand, had a minimal effect on the supralinear response. Taken together, these results delineate the roles for SST and PV neurons in active synaptic integration. Differential effects of inhibition by SST and PV interneurons likely increase the computational capacity of the pyramidal neurons in modulating the nonlinear integration of synaptic output.
Significance Statement
The principal function of neurons is to integrate a barrage of synaptic inputs and convert them into spike output. Such integration of inputs in the sensory neocortex ensures the transformation of environmental stimuli into a meaningful perception of the outside world. Synaptic integration in neuronal dendrites is shaped by passive electrical properties, active voltage-gated mechanisms, and inhibition from interneurons. Our results show that two genetically distinct subtypes of interneurons exert different types of inhibitory influence on active dendritic integration. Subtype-specific inhibitory influences provide a modulatory repertoire for the single cell computations that occur during synaptic integration.
Footnotes
The authors declare no competing financial interests.
This work was supported by NIH grant R01NS091335, NSF grant 1707287, the Human Frontier Science Program, the Klingenstein Foundation, and the Simons Foundation (to S.L.S), NIH grant R01NS114086 (to B.D.P.), and Helen Lyng White Fellowship (to I.T.S). We thank Paul Manis, Matthew Judson, and Joseph Canzano for helpful discussions and for providing valuable comments on the earlier versions of this manuscript.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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