Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins.

TitleSox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins.
Publication TypeJournal Article
Year of Publication2021
AuteursLuppi, MPereira, Azcorra, M, Caronia-Brown, G, Poulin, J-F, Gaertner, Z, Gatica, S, Moreno-Ramos, OAndrés, Nouri, N, Dubois, M, Ma, YC, Ramakrishnan, C, Fenno, L, Kim, YSeok, Deisseroth, K, Cicchetti, F, Dombeck, DA, Awatramani, R
JournalCell Rep
Volume37
Issue6
Pagination109975
Date Published2021 11 09
ISSN2211-1247
KeywordsAged, Aged, 80 and over, Animals, Case-Control Studies, Corpus Striatum, Dopamine, Dopaminergic Neurons, Female, Gene Expression Regulation, Developmental, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Parkinson Disease, SOXD Transcription Factors, Substantia Nigra, Ventral Tegmental Area
Abstract

Dopamine (DA) neurons in the ventral tier of the substantia nigra pars compacta (SNc) degenerate prominently in Parkinson's disease, while those in the dorsal tier are relatively spared. Defining the molecular, functional, and developmental characteristics of each SNc tier is crucial to understand their distinct susceptibility. We demonstrate that Sox6 expression distinguishes ventrally and dorsally biased DA neuron populations in the SNc. The Sox6 population in the ventral SNc includes an Aldh1a1 subset and is enriched in gene pathways that underpin vulnerability. Sox6 neurons project to the dorsal striatum and show activity correlated with acceleration. Sox6 neurons project to the medial, ventral, and caudal striatum and respond to rewards. Moreover, we show that this adult division is encoded early in development. Overall, our work demonstrates a dual origin of the SNc that results in DA neuron cohorts with distinct molecular profiles, projections, and functions.

DOI10.1016/j.celrep.2021.109975
Alternate JournalCell Rep
PubMed ID34758317
PubMed Central IDPMC8607753
Grant ListP50 DA044121 / DA / NIDA NIH HHS / United States
R21 NS092034 / NS / NINDS NIH HHS / United States
R01 MH110556 / MH / NIMH NIH HHS / United States
R01 NS119690 / NS / NINDS NIH HHS / United States
R01 NS096240 / NS / NINDS NIH HHS / United States
F31 NS122481 / NS / NINDS NIH HHS / United States
R01 MH110555 / MH / NIMH NIH HHS / United States