Connectomic analysis of thalamus-driven disinhibition in cortical layer 4

• DOI: 10.1016/j.celrep.2022.111476
• Publication Date: 2022-10-11T15:13:32Z
• Authors: Yunfeng Hua; Sahil Loomba; Verena Pawlak; Kay-Michael Voit; Philip Laserstein; Kevin M. Boergens; Damian J. Wallace; Jason N.D. Kerr; Moritz Helmstaedter
• Keywords: Neurons; Thalamus; Interneurons; Pyramidal Cells; Connectome

Sensory signals are transmitted via the thalamus primarily to layer 4 (L4) of the primary sensory cortices. While information about average neuronal connectivity in L4 is available, its detailed higher-order circuit structure is not known. Here, we used three-dimensional electron microscopy for a connectomic analysis of the thalamus-driven inhibitory network in L4. We find that thalamic input drives a subset of interneurons with high specificity, which in turn target excitatory neurons with subtype specificity. These interneurons create a directed disinhibitory network directly driven by the thalamic input. Neuronal activity recordings show that strong synchronous sensory activation yields about 1.5-fold stronger activation of star pyramidal cells than spiny stellates, in line with differential windows of opportunity for activation of excitatory neurons in the thalamus-driven disinhibitory circuit model. With this, we have identified a high degree of specialization of the microcircuitry in L4 of the primary sensory cortex.