Dopaminergic neurons are not a major Sonic hedgehog ligand source for striatal cholinergic or PV interneurons

• Published in: iScience Vol. 25; no. 11; p. 105278
• Main Authors: Turcato, Flavia Correa, Wegman, Elliot, Lu, Tao, Ferguson, Nathan, Luo, Yu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.11.2022; Elsevier
• Subjects: biological sciences; cellular neuroscience; Natural sciences; neuroscience; Natural sciences; neuroscience; biological sciences; cellular neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105278

A model was previously proposed that DA neurons provide SHH ligand to striatal interneurons, which in turn support the survival of DA neurons through the release of trophic factors such as Glial cell-derived neurotrophic factor (GDNF). However, some key clinical observations do not support this proposed model, and a recent independent study shows that striatal cholinergic neuron survival does not rely on intact DA neuron projections. To resolve this discrepancy, we generated several independent mouse lines to examine the exact role of DA neuron-derived Shh signaling in the maintenance of the basal ganglia circuit and to identify the Shh-producing cells in the adult brain. Our data suggest that the deletion of Shh in DA neurons does not affect DA neuron survival or locomotive function in cKO mice during aging, nor does it affect the long-term survival of cholinergic or FS PV + interneurons in the striatum (STR). [Display omitted] •Shh-expressing neurons are identified in multiple brain regions•Dopaminergic neurons are not Shh-expressing neurons in the adult mouse brain•Dopaminergic Shh deletion does not affect striatal PV or cholinergic neuron survival Natural sciences; Biological sciences; Neuroscience; Cellular neuroscience.