PT  - JOURNAL ARTICLE
AU  - N. Frezel
AU  - E. Platonova
AU  - F.F. Voigt
AU  - J.M. Mateos
AU  - R. Kastli
AU  - U. Ziegler
AU  - T. Karayannis
AU  - F. Helmchen
AU  - H. Wildner
AU  - H.U. Zeilhofer
TI  - In-depth characterization of layer 5 output neurons of the primary somatosensory cortex innervating the mouse dorsal spinal cord
AID  - 10.1101/2020.04.02.021311
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.02.021311
4099  - http://biorxiv.org/content/early/2020/05/11/2020.04.02.021311.short
4100  - http://biorxiv.org/content/early/2020/05/11/2020.04.02.021311.full
AB  - Neuronal circuits of the spinal dorsal horn integrate sensory information from the periphery with inhibitory and facilitating input from higher CNS areas. Most previous work focused on projections descending from the hindbrain. Less is known about inputs descending from the cerebral cortex. Here, we identified cholecystokinin (CCK) positive layer 5 pyramidal neurons of the primary somatosensory cortex (CCK+ S1-CST neurons) as a major source of input to the spinal dorsal horn. We combined intersectional genetics and virus-mediated gene transfer to characterize CCK+ S1-CST neurons and to define their presynaptic input and postsynaptic target neurons. We found that S1-CST neurons constitute a heterogeneous population that can be subdivided into distinct molecular subgroups. Rabies-based retrograde tracing revealed monosynaptic input from layer 2/3 pyramidal neurons, from parvalbumin (PV) positive cortical interneurons, and from thalamic relay neurons in the ventral posterolateral nucleus. WGA-based anterograde tracing identified postsynaptic target neurons in dorsal horn laminae III and IV. About 60% of these neurons were inhibitory and about 60% of all spinal target neurons expressed the transcription factor c-Maf. The heterogeneous nature of both S1-CST neurons and their spinal targets suggest complex roles in the fine-tuning of sensory processing.Competing Interest StatementThe authors have declared no competing interest.CSTcorticospinal tractrAAVrecombinant adeno-associated virusRVMrostral ventromedial medullaS1primary somatosensory cortexS1hlhindlimb area of S1S1-CSTcorticospinal tract originating in S17Nfacial nucleiACCanterior cingulate cortexMnRmedian raphe nucleusPAGPeriaqueductal greyS1hlsomatosensory cortexhindlimb area.VPLventral posterolateral nucleus of the thalamusWGAwheat germ agglutininCpudorsal striatum.