Targeting and driving somatosensory neurons

Sammanfattning: Pain and itch are two distinct sensations, but the fundamental question of how our nervous system distinguishes the processing and encoding of their related information is still far to be clearly delineated. At the spinal cord level, evidences have pointed out specific groups of neurons expressing the gastrin releasing peptide (Grp) and its receptor (Grpr) as responsible for carrying specifically itch-related information. Such important findings suggest a labeled line for itch and hypothesize the existence of separate pathways transmitting different sensory modalities already at this stage. Aiming at digging further on the pain/itch dualism, the present thesis focused first in addressing the GRPR-expressing dorsal horn interneurons and its roles in itch transmission. In the paper I, we observed that this population is composed mainly by excitatory interneurons, transmits itch through glutamate, and is at least partly downstream to the natriuretic peptide b (NPPB) signaling. Interestingly, increasing amount of behavior evidences have suggested that itch-related information is under local inhibition in the dorsal horn, since decrease of the local inhibitory tone by the peptide somatostatin is able to potentiate itch sensation in mice. In the paper II we complement these findings by showing in vitro that the itch-related GRPR-expressing dorsal horn neurons are under local tonic and phasic inhibition, besides being partly activated by somatostatin, corroborating that this population is indeed part of the disinhibition-induced itch circuitry. In order to confirm the itch-specific phenotype related to GRPR-expressing neurons and extend this theory to the rodent orofacial area, in the paper III we showed a new method developed to target and manipulate the orofacial-related trigeminal neurons. By using this method, we unexpectedly observed a functional switch in the GRPR population, from itch-related in the spinal cord to pain-related in the trigeminal nucleus caudalis, suggesting a labeled line of orofacial pain in this brainstem nucleus. As in the trigeminal nuclei, neuronal circuitry formed by defined cell types transmitting pain- and itch-related information has not been addressed yet in the somatosensory cortex. In the paper IV, we offer a mouse genetic tool that enables the target of barrel field spiny stellate cells, opening for more detailed knowledge of cortical circuitry encoding somatosensory information. In summary, the present thesis brings both complementary findings and new intriguing insights on how our nervous system transmits somatosensory stimuli from different modalities, paving basic knowledge on the mechanisms that build pain and itch as distinct percepts.