RRC ID 57558
Author Wu J, Kung J, Dong J, Chang L, Xie C, Habib A, Hawes S, Yang N, Chen V, Liu Z, Evans R, Liang B, Sun L, Ding J, Yu J, Saez-Atienzar S, Tang B, Khaliq Z, Lin DT, Le W, Cai H.
Title Distinct Connectivity and Functionality of Aldehyde Dehydrogenase 1a1-Positive Nigrostriatal Dopaminergic Neurons in Motor Learning.
Journal Cell Rep
Abstract Parkinson's disease causes the most profound loss of the aldehyde dehydrogenase 1A1-positive (ALDH1A1+) nigrostriatal dopaminergic neuron (nDAN) subpopulation. The connectivity and functionality of ALDH1A1+ nDANs, however, remain poorly understood. Here, we show in rodent brains that ALDH1A1+ nDANs project predominantly to the rostral dorsal striatum, from which they also receive most monosynaptic inputs, indicating extensive reciprocal innervations with the striatal spiny projection neurons (SPNs). Functionally, genetic ablation of ALDH1A1+ nDANs causes severe impairments in motor skill learning, along with a reduction in high-speed walking. While dopamine replacement therapy accelerated walking speed, it failed to improve motor skill learning in ALDH1A1+ nDAN-ablated mice. Altogether, our study provides a comprehensive whole-brain connectivity map and reveals a key physiological function of ALDH1A1+ nDANs in motor skill acquisition, suggesting the motor learning processes require ALDH1A1+ nDANs to integrate diverse presynaptic inputs and supply dopamine with dynamic precision.
Volume 28(5)
Pages 1167-1181.e7
Published 2019-7-30
DOI 10.1016/j.celrep.2019.06.095
PII S2211-1247(19)30881-2
PMID 31365862
PMC PMC6741442
MeSH Aldehyde Dehydrogenase 1 Family / genetics Aldehyde Dehydrogenase 1 Family / metabolism* Animals Corpus Striatum / cytology Corpus Striatum / metabolism* Dopamine / metabolism Dopaminergic Neurons / cytology Dopaminergic Neurons / metabolism* Learning* Mice Mice, Transgenic Retinal Dehydrogenase / genetics Retinal Dehydrogenase / metabolism* Substantia Nigra / metabolism*
IF 7.815
Times Cited 5
DNA material B6N Mouse BAC clone (RDB07573) B6Ng01-066I24