Connectomic analysis of thalamus-driven disinhibition in cortical layer 4

Cell Rep. 2022 Oct 11;41(2):111476. doi: 10.1016/j.celrep.2022.111476.


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.

Keywords: CP: Neuroscience; circuits; connectomics; disinhibition; electron microscopy; inhibition; sensory cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Connectome*
  • Interneurons / physiology
  • Neurons / physiology
  • Pyramidal Cells / physiology
  • Thalamus / physiology