Two major types of striatopallidal projection neurons have been found in the basal ganglia: 1) those containing substance P (SP), dynorphin (DYN) and GABA; and 2) those containing enkephalin (ENK) and GABA. The proposed studies will determine the morphological and connectional differences that might underlie the differences between these neuronal populations in terms of their role in motor functions. The studies will be conducted in pigeons, in whom these striatopallidal neurons can readily and unambiguously be identified by their topographic location in the striatum. In one study, the relative percentages of the SP+ and ENK+ striatopallidal neurons will be determined, using retrograde labeling of striatopallidal neurons with fluorogold in combination with immunofluorescence labeling for SP and ENK. A second study will determine if the two types of striatopallidal neurons innervate pallidal neurons that project to different targets, using fluorogold to retrogradely label target-specific populations of pallidal neurons and immunofluorescence to label the SP+ and ENK+ terminals. Two final lines of study will examine at the LM and EM levels whether these two different types of striatopallidal neurons differ in terms of the relative abundance, morphological characteristics and/or somal and dendritic distribution of the inputs from the substantia nigra and cortex. Nigral inputs to the striatum will be anterogradely labeled by PHA-L injections into the substantia nigra or by immunohistochemical labeling for tyrosine hydroxylase. Cortical inputs will be visualized by anterograde labeling after PHA-L injections into cortex or by the degenerative changes observable (at the EM level) after cortical lesions. In tissue from both lines of study, SP+ striatopallidal neurons will be labeled immunohistochemically in some sections and ENK+ striatopallidal neurons in others, using a different marker than used to label the nigrostriatal and corticostriatal terminals. Since striatal organization is very similar in all amniote species, these studies will aid in understanding the nature and anatomical basis of the functional differences between these two types of striatopallidal projection neurons in the control of movement. Further, since these populations are affected in Huntington's Disease and Parkinson's Disease, these studies may aid in understanding the motor impairments observed in these neurodegenerative disorders of the basal ganglia.
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