Aldehyde dehydrogenase 1\u2013positive nigrostriatal dopaminergic fibers exhibit distinct projection pattern and dopamine release dynamics at mouse dorsal striatum

Carmelo Sgobio,Armando G Salinas,Huaibin Cai,David M Lovinger,Xi Chen,Junbing Wu,Jing Pan,Wang Zheng,Margaret I Davis

doi:10.1038/s41598-017-05598-1

Abstract

Aldehyde dehydrogenase 1 (ALDH1A1)–positive dopaminergic (DA) neurons at the ventral substantia nigra pars compacta (SNpc) preferentially degenerate in Parkinson’s disease (PD). Their projection pattern and dopamine release properties, however, remains uncharacterized. Here we show that ALDH1A1–positive axons project predominantly to the rostral two–thirds of dorsal striatum. A portion of these axons converge on a small fraction of striosome compartments restricted to the dorsolateral striatum (DLS), where less dopamine release was measured compared to the adjacent matrix enriched with the ALDH1A1–negative axons. Genetic ablation of Aldh1a1 substantially increases the dopamine release in striosomes, but not in matrix. Additionally, the presence of PD-related human α-synuclein A53T mutant or dopamine transporter (DAT) blockers also differentially affects the dopamine output in striosomes and matrix. Together, these results demonstrate distinct dopamine release characteristics of ALDH1A1–positive DA fibers, supporting a regional specific function of ALDH1A1 in regulating dopamine availability/release in striatum.

Highlights

ALDH1A1 belongs to a large family of aldehyde dehydrogenases that oxidize a variety of reactive aldehyde species[1]
Previous neuron tracing studies suggest that DA neurons at the ventral tier of substantia nigra pars compacta (SNpc) send their axons to the striosome compartment of dorsal striatum[9]
Since ALDH1A1 is predominantly expressed by the ventral SNpc DA neurons in the brain[2, 8, 19, 20], we stained sequential coronal sections of 1–month–old wild-type C67BL6 mice to examine the projection pattern of ALDH1A1–positive SNpc axon fibers at the striatum using antibodies against ALDH1A1, the striosomal marker MOR1, and the DA axon terminal marker tyrosine hydroxylase (TH)

Summary

Introduction

ALDH1A1 belongs to a large family of aldehyde dehydrogenases that oxidize a variety of reactive aldehyde species[1]. Little is known about the connectivity and functionality of this group of neurons It is unclear whether the axons of these ALDH1A1–expressing DA neurons terminate at distinct locations at the dorsal striatum and exhibit different dopamine release dynamics. Previous neuron tracing studies suggest that DA neurons at the dorsal tier of SNpc project to the matrix compartment of dorsal striatum, whereas neurons at the ventral tier send their axons to the complementary striosome or patch compartment[9]. Type B fibers are from the ventral tier DA neurons and terminate predominantly in the striosomes. Dopamine release appears to be different in the striosome and matrix compartments of dorsal striatum[16]. The goal of the present study aims to determine the projection pattern and dopamine release properties of ALDH1A1–positive DA axons at the dorsal striatum. Since overexpression of PD-related α-synuclein A53T missense mutation substantially impairs dopamine release at the striatum[18], we examined whether DA release at ALDH1A1–positive and –negative axon terminals are differentially affected by mutant α-synuclein

Methods

Results

Conclusion