Cortico-thalamo-cortical circuits of mouse forelimb S1 are organized primarily as recurrent loops

Cortical projections to thalamus arise from corticothalamic (CT) neurons in layer 6 and pyramidal tract type (PT) neurons in layer 5B. We dissected the excitatory synaptic connections in somatosensory thalamus formed by CT and PT neurons of primary somatosensory (S1) cortex, focusing on mouse forelimb S1. Mice of both sexes were studied. The CT neurons in S1 synaptically excited S1-projecting thalamocortical (TC) neurons in subregions of both the ventral posterior lateral (VPL) and posterior (PO) nuclei, forming a pair of recurrent cortico-thalamo-cortical (C-T-C) loops. The PT neurons in S1 also formed a recurrent loop with S1-projecting TC neurons in the same subregion of PO. The PT neurons in adjacent primary motor (M1) cortex formed a separate recurrent loop with M1-projecting TC neurons in a nearby subregion of PO. Collectively, our results reveal that C-T-C circuits of mouse forelimb S1 are primarily organized as multiple cortical cell-type- and thalamic subnucleus-specific recurrent loops, with both CT and PT neurons providing strongest excitatory input to TC neurons that project back to S1. The findings, together with those of related studies of C-T-C circuits, thus suggest that recurrently projecting thalamocortical neurons are the principal targets of cortical excitatory input to mouse somatosensory and motor thalamus. SIGNIFICANCE STATEMENT Bidirectional cortical communication with thalamus is considered an important aspect of sensorimotor integration for active touch in the somatosensory system, but the cellular organization of the circuits mediating this process is not well understood. We used an approach combining cell-type-specific anterograde optogenetic excitation with single-cell recordings targeted to retrogradely labeled thalamocortical neurons to dissect these circuits. The findings reveal a consistent pattern: cortical projections to somatosensory thalamus target thalamocortical neurons that project back to the same cortical area. Commonalities of these findings to previous descriptions of related circuits in other areas suggest that C-T-C circuits may generally be organized primarily as recurrent loops.