Calretinin and Calbindin neurons are correctly positioned in the superficial dorsal horn of Reeler mutants whereas many Gastrin-Releasing Peptide neurons co-express Reelin and may be influenced by Reelin signaling

The Reelin-signaling pathway is vital for correct neuronal positioning in the central nervous system. Adult mice with the deletion of Reelin or Disabled-1 (Dab1) display an increased threshold for mechanical pain and decreased threshold for thermal pain. Previous studies found anatomical alterations in the pain-processing areas of the dorsal horn, and that a number of these neurons express Reelin or Dab1, implying that they are under the influence of the Reelin-signaling pathway. Wang et al. (2019) reported that Neurokinin-1 receptor-expressing neurons are mispositioned in the superficial dorsal horn and contribute to the hypersensitivity of Reln-/- mice to thermal heat. The overall aim of my project is to discover if the Calretinin neurons, implicated in processing mechanical pain, and the generally excitatory Calbindin neurons are mispositioned in the superficial dorsal horn and likely contribute to mechanical hyposensitivity of Reln-/- mice. We found, however, that Calretinin and Calbindin neurons are not mispositioned in the superficial dorsal horn of Reln-/- mice. Along with pain, itch is a related major somatosensory sensation. Recently, we determined that dab1 mutants show reduced scratching behavior compared to wild-type mice, and we hypothesize that mispositioned Gastrin-releasing peptide (GRP)-expressing neurons likely contribute to this phenotype. GRP is well known to be involved in transmitting itch signals, and based on a single cell sequencing study, Haring et al. (2018) reported that Reelin and GRP are highly expressed together in two glutamatergic populations in laminae I-II. Our preliminary data show that 41% of GRP neurons in the superficial dorsal horn express Reelin in wild-type mice. Future studies will determine if GRP neurons also express Dab1 and whether GRP neurons are mispositioned in both Reln and dab1 mutant mice