Connectomic analysis of thalamus-driven disinhibition in cortical layer 4

• Published in: Cell reports (Cambridge) 2022-10, Vol.41 (2), p.111476-111476, Article 111476
• Main Authors: Hua, Yunfeng, Loomba, Sahil, Pawlak, Verena, Voit, Kay-Michael, Laserstein, Philip, Boergens, Kevin M., Wallace, Damian J., Kerr, Jason N.D., Helmstaedter, Moritz
• Format: Article
• Language: English
• Subjects: circuits; connectomics; disinhibition; electron microscopy; inhibition; sensory cortex
• ISSN: 2211-1247; 2211-1247
• 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. [Display omitted] •Thalamus directly drives a disinhibitory circuit in cortical layer 4•Distinct interneuron input to excitatory neuron subtypes in layer 4•Temporally precise windows of activation within layer 4 predicted from connectome•Functional recordings support such differential activation windows within layer 4 Hua et al. used three-dimensional electron microscopy to determine the inhibitory interneuron connectome within layer 4 of mouse primary somatosensory cortex, discovering a directly thalamus-driven disinhibitory circuitry with target specificity for the excitatory neuronal subtypes. Functional recordings confirm the differential temporal activation windows created by this circuit.