Control of the Nigrostriatal Pathway by the Tail of the Ventral Tegmental Area
Rapid Response Innovation Awards, 2013
Neuroanatomical inputs to the substantia nigra pars compacta (SNc) modulate the activity of dopamine neurons and could influence the symptoms of Parkinson’s disease. A new brain structure was recently described — the tail of the ventral tegmental area (tVTA) — that exerts an inhibitory control on the activity of SNc dopamine neurons. This project explores the consequences of suppressing tVTA inhibition of SNc neurons on motor performance in a model of Parkinson’s disease.
Bilateral tVTA lesion will allow chronic silencing of this brain region in a pre-clinical model. The effects of such suppression will be explored both on the neuronal activity of SNc neurons and on motor coordination and motor skill learning. This influence will be assessed in a pre-clinical model of partial dopamine loss, to test for improvement of the motor impairments.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Improving the symptoms of Parkinson’s disease remains a challenge requiring new molecular, cellular or neuroanatomical targets. By studying the functional consequences of suppressing a main brake of dopamine systems, the results will allow assessing whether tVTA could be a potential target for motor improvement in Parkinson’s disease.
Researchers hypothesize that suppressing the activity of the tVTA may improve motor performances by releasing SNc dopamine neurons from a major inhibitory brake. This would suggest that tVTA manipulation could modulate symptoms of parkinsonism. If it is the case, it would warrant further research to characterize this new brain area in humans and to explore its potential as treatment target.
Research Director at Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique
Location: Strasbourg, France