Figure 2.

Presynaptic inputs alter the firing pattern of ALDH1A1-positive SNc DANs, in which the burst firing recruits dopamine for ATP production: (A) We outline the locations of major input neurons in the brain that directly innervate ALDH1A1-positive SNc DANs. While the ALDH1A1-positive SNc DANs integrate diverse synaptic inputs from different brain regions, they provide the output mainly to the dorsal striatum. The size of the circles represents the percentage of overall inputs. (B) Presynaptic inputs regulate the transition from tonic firing to burst firing of ALDH1A1-positive SNc DANs. (C) Cytosolic dopamine can be oxidized by mitochondria-attached MAO to produce H₂O₂ and DOPAL. H₂O₂ can be used for Complex IV-mediated ATP production, while the cytotoxic byproduct DOPAL can be neutralized by ALDH1A1. The increase of ATP production may lead to increased dopamine release and reuptake, resulting in further increase of ATP production and dopamine release during the burst firing. DS: Dorsal striatum; ZI: zona incerta; NAcb.C: nucleus accumbens core; NAcb.S: nucleus accumbens shell; MO: motor cortex; SS1: somatosensory cortex; VP: ventral pallidum; GPe: globus pallidus; STN: subthalamic nucleus; PAG: periaqueductal gray; APN: anterior pretectal nucleus; MRN: medial raphe nucleus; PRNr: pontine reticular nucleus roastral; PPN: posterior pretectal nucleus; PCG: pontine central gray; SCm: superior colliculus medial; DRN: dorsal raphe nucleus; CEA: central nucleus of the amygdala; LHA: lateral hypothalamus; PB: pontine parabrachial nucleus.