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

Cortical projections to the 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 the somatosensory thalamus formed by CT and PT neurons of the primary somatosensory (SI) cortex, focusing on mouse forelimb SI. Mice of both sexes were studied. The CT neurons in SI synaptically excited Sl- projecting thalamocortical (TC) neurons in subregions of both the ventral posterior lateral and posterior (PO) nuclei, forming a pair of recurrent cortico-thalamo-cortical (C-T -C) loops. The PT neurons in SI also formed a recurrent loop with S1-projecting TC neurons in the same subregion of the PO. The PT neurons in the adjacent primary motor (M1) cortex formed a separate recurrent loop with M1-projecting TC neurons in a nearby subregion of the PO. Collectively, our results reveal that C-T-C circuits of mouse forelimb SI are primarily organized as multiple cortical cell-type-specific and thalamic subnucleus-specific recurrent loops, with both CT and PT neurons providing the strongest excitatory input to TC neurons that project back to SI. 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 the mouse somatosensory and motor thalamus.