Functional Anatomy of the Basal Ganglia

Grofova, Irena

Abstract

The substantia nigra is implicated in the neostriatal control of posture and movement, and it is the locus of primary defect in Parkinsonian patients. This nucleus is a major target of neostriatal efferents and it in turn projects back to the neostraitum as well as to several subcortical regions (i.e. thalamus, optic tectum, ponto-mesencephalic reticular substance) which are involved in the integration of sensorimotor activities. The proposed experiments will utilize the electrophysiological technique of intracellular recording and labeling of the recorded neurons with horseradish peroxidase (HRP) to study two important aspects of the rodent substantia nigra (SN): 1) The morphology and relationship of SN neurons projecting to different target nuclei. 2) Direct synaptic input from the neostriatum to these neurons. More specifically in the first set of experiments, nigrostriatal, nigrothalamic and nigrotectal neurons will be identified by intracellularly recording antidromic potentials and by subsequent labeling of the cells with HRP. The dendritic and axonal morphology of these cells will be analyzed using both light and electron microscopic methods with special regard for the intrinsic circuitry of these cells via axon collaterals and possibly dendro-dendritic synapses. The second set of experiments will employ intracellular HRP injections in combination with chemical lesions of the neostriatum in order to examine the termination of the major extrinsic afferent feedback system of the SN, namely the striatal afferents. The presence and distribution of degenerating striatal terminals on single nigral projection neurons (i. e. nigrostriatal, nigrothalamic and nigrotectal neurons) will be established with the electron microscope. These data will provide an essential framework for the understanding of the circuitries through which the basal ganglia control posture and movement under normal and pathological circumstances. Such an understanding, in light of concurrent pharmacological advances in drug therapy, should contribute to the successful treatment of basal ganglia related motor and mental disorders.