Abstract
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 descending projections originating from the hindbrain. Less is known about the organisation of inputs descending from the cerebral cortex. Here, we identified cholecystokinin (CCK) positive layer 5 pyramidal neurons of the primary somatosensory cortex (S1-CST neurons) as a major source of descending 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) and neuropeptide Y (NPY) 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 sophisticated roles in the fine-tuning of sensory processing.
Abbreviations
- CST
- corticospinal tract
- rAAV
- recombinant adeno-associated virus
- RVM
- rostral ventromedial medulla
- S1
- primary somatosensory cortex
- S1hl
- hindlimb area of S1
- S1-CST
- corticospinal tract originating in S1
- 7N
- facial nuclei
- ACC
- anterior cingulate cortex
- MnR
- median raphe nucleus
- PAG
- Periaqueductal grey
- S1hl
- somatosensory cortex, hindlimb area
- VPL
- ventral posterolateral nucleus of the thalamus
- WGA
- wheat germ agglutinin.