Connectomic analysis of thalamus-driven disinhibition in cortical layer 4

ABSTRACT In mammals, sensory signals are transmitted via the thalamus primarily to layer 4 of the primary sensory cortices. While information about average neuronal connectivity in this layer is available, the detailed and higher-order circuit structure is not known. Here, we used 3-dimensional electron microscopy for a connectomic analysis of the thalamus-driven inhibitory network in a layer 4 barrel. We find that thalamic input drives a subset of interneurons with high specificity. These interneurons in turn target spiny stellate and star pyramidal excitatory neurons with subtype specificity. In addition, they create a directed disinhibitory network directly driven by the thalamic input. Together, this circuit can create differential windows of opportunity for activation of the types of excitatory neurons in dependence of strength and timing of thalamic input. With this, we have identified a so-far unknown degree of specialization of the microcircuitry in the main thalamocortical recipient layer of the primary sensory cortex.