Ventral tegmental area

Abstract: Parkinson's disease is characterized by abundant α-synuclein (α-Syn) neuronal inclusions, known as Lewy bodies and Lewy neurites, and the massive loss of midbrain dopamine neurons. However, a cause-and-effect relationship between Lewy inclusion formation and neurodegeneration remains unclear. Here, we found that in wild-type nontransgenic mice, a single intrastriatal inoculation of synthetic α-Syn fibrils led to the cell-to-cell transmission of pathologic α-Syn and Parkinson's-like Lewy pathology in anatomically interconnected regions. Lewy pathology accumulation resulted in progressive loss of dopamine neurons in the substantia nigra pars compacta, but not in the adjacent ventral tegmental area, and was accompanied by reduced dopamine levels culminating in motor deficits. This recapitulation of a neurodegenerative cascade thus establishes a mechanistic link between transmission of pathologic α-Syn and the cardinal features of Parkinson's disease.

Abstract: We develop a theoretical framework that shows how mesencephalic dopamine systems could distribute to their targets a signal that represents information about future expectations. In particular, we show how activity in the cerebral cortex can make predictions about future receipt of reward and how fluctuations in the activity levels of neurons in diffuse dopamine systems above and below baseline levels would represent errors in these predictions that are delivered to cortical and subcortical targets. We present a model for how such errors could be constructed in a real brain that is consistent with physiological results for a subset of dopaminergic neurons located in the ventral tegmental area and surrounding dopaminergic neurons. The theory also makes testable predictions about human choice behavior on a simple decision-making task. Furthermore, we show that, through a simple influence on synaptic plasticity, fluctuations in dopamine release can act to change the predictions in an appropriate manner.