Destruction or dysfunction of the dopaminergic neurons of the mesencephalon is believed to underly a variety of disorders of movement, motivation and mentation, including Parkinson's disease, and schizophrenia. In those disorders not accompanied by death of the dopaminergic neurons, it is likely that a disruption of the activity patterns of those neurons is an important component of the pathology. Dopaminergic neurons fire in stereotyped modes, controlled largely by calcium currents and by calcium-dependent potassium currents. The investigators will employ calcium-imaging of single neurons injected intracellularly with calcium indicator during whole cell recording in slices visualized by infra-red DIC microscopy. This will allow simultaneous detection of membrane potential at the cell bodies of the dopaminergic neurons and detection of calcium entry in the cell body and dendritic tree. Current models of firing pattern generation by dopaminergic neurons differ in their prediction of the location of calcium entry, and our experiments allow a critical test of these models. In addition to their role in generating firing patterns, calcium currents in dopaminergic neurons control the release of dopamine from dendritic stores. Dendritic dopamine release function to regulate overall activity of dopaminergic neurons in the region and may modulate the release of other transmitters. They will issue fast-scan cyclic voltammentry to detect dopamine release form individual dendrites of identified dopaminergic neurons while examining calcium entry in the same dendrite as described above. This will allow direct comparison of calcium entry and dopamine release at particular positions along single dendrites of neurons whose firing is controlled by a somatic electrode. Finally, synaptic excitation and local dendrite excitation by applied glutamate will be used to test for the local control of dendritic calcium and dopamine release by subthreshold excitatory currents.
| Wilson, C J; Callaway, J C (2000) Coupled oscillator model of the dopaminergic neuron of the substantia nigra. J Neurophysiol 83:3084-100 |
