In addition to releasing dopamine from nerve terminals in striatum, nigrostriatal dopamine neurons are also capable of releasing dopamine from somatodendritic regions in substantia nigra. These two processes share fundamental similarities including calcium-dependence, voltage- sensitivity and storage in vesicles. While the biological mechanisms of release in both regions are similar, it is unknown to what extent somatodendritic and nerve terminal release are coupled to one another. While nerve terminal release and impulse activity are highly correlated, it is unknown to what magnitude nerve impulse activity generated in the initial segment affects dopamine release in the dendrites. In addition, much is known about the effects of neurochemical and neuroanatomical afferents on dopamine release from axon terminals, however, this has never been examined systematically for somatodendritic release in substantia nigra. In order to investigate this further, in vivo microdialysis coupled to electrochemical detection will be used to measure the effects of manipulation of glutamate and GAGA neurotransmission within substantia nigra as well as alterations in the afferent input from subthalamic nucleus and globus pallidus to substantia nigra under normal conditions and after systemic haloperidol administration on somatodendritic dopamine efflux. In the final set of experiments, extracellular recording of dopamine neurons combined with measurement of nigral dopamine efflux by microdialysis will be performed in order to study the relationship between nerve impulse activity and somatodendritic dopamine release.
