Neocortical Somatostatin-Expressing GABAergic Interneurons Disinhibit the Thalamorecipient Layer 4

Abstract

SUMMARY Subtypes of GABAergic interneurons (INs) are crucial for cortical function, yet their specific roles are largely unknown. In contrast to supra- and infra-granular layers, where most somatostatin-expressing (SOM) INs are layer 1-targeting Martinotti cells, the axons of SOM INs in layer 4 somatosensory cortex largely remain within layer 4. Moreover, we found that whereas layers 2/3 SOM INs target mainly pyramidal cells (PCs), layer 4 SOM INs target mainly fast-spiking (FS) INs. Accordingly, optogenetic inhibition of SOM INs in an active cortical network increases the firing of layers 2/3 PCs whereas decreases the firing of layer 4 principal neurons (PNs). This unexpected effect of SOM INs on layer 4 PNs occurs via their inhibition of local FS INs. These results reveal a novel disinhibitory microcircuit in the thalamorecipient layer through interactions among subtypes of GABAergic INs, and suggest that SOM IN-mediated disinhibition represents an important circuit mechanism for cortical processing.

Control of response reliability by parvalbumin-expressing interneurons in visual cortex

“…1). As the same type of GABAergic interneurons in different cortical layers can exhibit different output connectivity and electrophysiological properties 50 , the function of inhibitory neurons is likely to depend on laminar location. It will be important for future studies to examine how interneuron subtypes in different cortical layers contribute to sensory processing.…”

Activation of cannabinoid system in anterior cingulate cortex and orbitofrontal cortex modulates cost-benefit decision making

“…Third, the interneurons might exert a more sophisticated control on the principal neurons output through a variety of synapses rather than a simply direct inhibition of principal neurons. Recently, there have been several studies demonstrating the importance of interneuroninterneuron interactions in the processing of cortical functions (Jiang et al 2013;Pfeffer et al 2013;Pi et al 2013;Xu et al 2013). These interactions, which consist of inhibition of inhibitory neurons, can lead to disinhibition of pyramidal cell activity by decreasing the net inhibitory drive on these neurons.…”

Impaired excitability of somatostatin- and parvalbumin-expressing cortical interneurons in a mouse model of Dravet syndrome

“…The following parameters were measured to characterize neuronal membrane properties: resting membrane potential (E m ) was recorded immediately after the rupture of the neuronal membrane; input resistance (R in ) was determined by measuring the voltage change in response to a small hyperpolarizing current pulse (−40 pA, 1 s) at E m ; membrane capacitance (C m ) was determined by a monoexponential fit to the voltage produced by a small hyperpolarizing current pulse (−40 pA, 1 s) at resting potential; rheobase was defined as the smallest rectangular current injection that elicited an AP; AP threshold was defined as the membrane potential at the point at which derivatives of voltage with respect to time = 10 mV/ms; AP amplitude was measured between threshold and AP peak; AP width was measured at half height between threshold and AP peak; the AP frequency adaptation ratio was defined as the ratio between the steady-state frequency (the reciprocal of the average of the last four interspike intervals) and the initial frequency (the reciprocal of the first four interspike intervals); the AP amplitude adaptation ratio was defined as the ratio of the steady-state amplitude (the average of the last four AP amplitudes) to the initial amplitude (the average of the first four AP amplitudes); protocols were adapted from ref. 25. Population data are presented as mean ± SEM.…”

“…However, selective deletion of Scn1a in neocortical PV interneurons failed to reproduce the effects of DS fully, suggesting the involvement of other subtypes of interneurons in this disease (23,24). Layer V Martinotti cells have ascending axons that arborize in layer I and spread horizontally to neighboring cortical columns, making synapses on apical dendrites of pyramidal neurons (17,25,26). They generate frequency-dependent disynaptic inhibition (FDDI) that dampens excitability of neighboring layer V pyramidal cells (27)(28)(29), contributing to maintenance of the balance of excitation and inhibition in the neocortex.…”