| This thesis focuses on the functional relationship between the subthalamic nucleus (STN) and the ventral pallidum (VP). The VP is part of the limbic system and involved in motivated behaviors. The STN is important in motor function. Changes in the relationship between the STN and VP may be involved in Parkinson's disease (PD), as PD patients develop altered motivational states in addition to motor symptoms.; The projection from the STN to the VP is hypothesized to be monosynaptic, and use excitatory amino acid (EAA) neurotransmission. Using in vivo extracellular electrophysiological recordings, it was found that electrical stimulation of the STN evoked action potentials in the VP with a very short latency, supporting the hypothesis that there is a monosynaptic projection. These excitatory responses were attenuated by microiontophoretic application of EAA antagonists.; To investigate whether the VP demonstrates altered EAA neurotransmission in a rat model of PD, we examined the VP three weeks after using the neurotoxin 6-OHDA to destroy dopaminergic neurons in the midbrain. Neurons in the VP in the lesioned hemisphere were much more sensitive to over-excitation by FAA's. Thus, neuronal physiology of VP neurons is altered in this model of PD.; As dopamine depletion altered VP sensitivity to EAA, the possibility was considered that this may reflect alterations in structures interacting with the VP. To test this hypothesis, the expression of the immediate early gene Fos was measured as a marker of neuronal activation in VP associated brain regions in the rat 6-OHDA model of PD. In control rats, intra-VP infusions of NMDA increased in the number of Fos-expressing neurons in both the VP and the STN. In the lesioned hemisphere, the STN response was attenuated. This finding suggests that the VP influence on the STN is blunted following long-term dopamine depletion.; In conclusion, the STN is known to be hyperactive in the parkinsonian state, and this occurs at a time when the VP is more vulnerable to the EAA transmission. Dopamine deafferentation diminishes the influence that the VP has on the STN. The novel findings of this thesis indicate previously undescribed adaptations that may contribute to parkinsonian symptomatology. |
