Effects of Electrically Coupled Inhibitory Networks on Local Neuronal Responses to Intracortical Microstimulation

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Abstract
Using in vivo multielectrode electrophysiology in mice, we investigated the underpinnings of a local, long-lasting firing rate suppression evoked by intracortical microstimulation. Synaptic inhibition contributes to this suppression as it was reduced by pharmacological blockade of γ-aminobutyric acid type B (GABAB) receptors. Blockade of GABAB receptors also abolished the known sublinear addition of inhibitory response duration after repetitive electrical stimulation. Furthermore, evoked inhibition was weaker and longer in connexin 36 knockout (KO) mice that feature decoupled cortical inhibitory networks. In supragranular layers of KO mice even an unusually long excitatory response (≤50 ms) appeared that was never observed in wild-type (WT) mice. Furthermore, the spread and duration of very fast oscillations (>200 Hz) evoked by microstimulation at a short latency were strongly enhanced in KO mice. In the spatial domain, lack of connexin 36 unmasked a strong anisotropy of inhibitory spread. Although its reach along layers was almost the same as that in WT mice, the spread across cortical depth was severely hampered. In summary, the present data suggest that connexin 36–coupled networks significantly shape the electrically evoked cortical inhibitory response. Electrical coupling renders evoked cortical inhibition more precise and strong and ensures a uniform spread along the two cardinal axes of neocortical geometry.