Endogenous dopamine transmission is crucial for motor skill recovery after stroke.

Ischemic stroke frequently causes motor impairments. Despite exercise can improve motor outcomes, many stroke survivors remain life-long disabled. Understanding the mechanisms associated with motor recovery after a stroke is necessary to develop treatments. Here, we show that endogenous DA transmission is required for optimal motor skill recovery following photothrombotic stroke in rats. Blockade of dopamine D1 and D2 receptors impaired the recovery of a forelimb reaching task and decreased the rats' motivation to complete full training sessions. Our data indicate that dopamine transmission is important to drive motor rehabilitation after stroke through motivational aspects and ultimately suggest that augmented motivation and reward feedback could be an interesting strategy to increase the effectiveness or rehabilitation.

Better Outcomes with Intranigral versus Intrastriatal Cell Transplantation: Relevance for Parkinson's Disease.

Intrastriatal embryonic ventral mesencephalon grafts have been shown to integrate, survive, and reinnervate the host striatum in clinical settings and in animal models of Parkinson's disease. However, this ectopic location does not restore the physiological loops of the nigrostriatal pathway and promotes only moderate behavioral benefits. Here, we performed a direct comparison of the potential benefits of intranigral versus intrastriatal grafts in animal models of Parkinson's disease. We report that intranigral grafts promoted better survival of dopaminergic neurons and that only intranigral grafts induced recovery of fine motor skills and normalized cortico-striatal responses. The increase in the number of toxic activated glial cells in host tissue surrounding the intrastriatal graft, as well as within the graft, may be one of the causes of the increased cell death observed in the intrastriatal graft. Homotopic localization of the graft and the subsequent physiological cell rewiring of the basal ganglia may be a key factor in successful and beneficial cell transplantation procedures.

Monoaminergic Modulation of Motor Cortex Function.

Elaboration of appropriate responses to behavioral situations rests on the ability of selecting appropriate motor outcomes in accordance to specific environmental inputs. To this end, the primary motor cortex (M1) is a key structure for the control of voluntary movements and motor skills learning. Subcortical loops regulate the activity of the motor cortex and thus contribute to the selection of appropriate motor plans. Monoamines are key mediators of arousal, attention and motivation. Their firing pattern enables a direct encoding of different states thus promoting or repressing the selection of actions adapted to the behavioral context. Monoaminergic modulation of motor systems has been extensively studied in subcortical circuits. Despite evidence of converging projections of multiple neurotransmitters systems in the motor cortex pointing to a direct modulation of local circuits, their contribution to the execution and learning of motor skills is still poorly understood. Monoaminergic dysregulation leads to impaired plasticity and motor function in several neurological and psychiatric conditions, thus it is critical to better understand how monoamines modulate neural activity in the motor cortex. This review aims to provide an update of our current understanding on the monoaminergic modulation of the motor cortex with an emphasis on motor skill learning and execution under physiological conditions.

Dopamine control of pyramidal neuron activity in the primary motor cortex via D2 receptors.

The primary motor cortex (M1) is involved in fine voluntary movements control. Previous studies have shown the existence of a dopamine (DA) innervation in M1 of rats and monkeys that could directly modulate M1 neuronal activity. However, none of these studies have described the precise distribution of DA terminals within M1 functional region nor have quantified the density of this innervation. Moreover, the precise role of DA on pyramidal neuron activity still remains unclear due to conflicting results from previous studies regarding D2 effects on M1 pyramidal neurons. In this study we assessed in mice the neuroanatomical characteristics of DA innervation in M1 using unbiased stereological quantification of DA transporter-immunostained fibers. We demonstrated for the first time in mice that DA innervates the deep layers of M1 targeting preferentially the forelimb representation area of M1. To address the functional role of the DA innervation on M1 neuronal activity, we performed electrophysiological recordings of single neurons activity in vivo and pharmacologically modulated D2 receptor activity. Local D2 receptor activation by quinpirole enhanced pyramidal neuron spike firing rate without changes in spike firing pattern. Altogether, these results indicate that DA innervation in M1 can increase neuronal activity through D2 receptor activation and suggest a potential contribution to the modulation of fine forelimb movement. Given the demonstrated role for DA in fine motor skill learning in M1, our results suggest that altered D2 modulation of M1 activity may be involved in the pathophysiology of movement disorders associated with disturbed DA homeostasis.