Resesarch in the Section on Neuroanatomy is concerned with the role of the basal ganglia in behavior. The basal ganglia receives inputs from all cortical areas, processes that input through the striatum, whose output pathways provide feedback, through the thalamus, to cortical areas involved in the selection and control of behavior. Our work focuses on two general questions of basal ganglia function. First, the organization of cortical input to the striatum, in order to understand what information the cortex provides to the basal ganglia? Second, to determine what the basal ganglia does with information from the cortex, which is essential to understand how the basal ganglia affects frontal cortical function. We address these questions in order to better establish how disorders of the basal ganglia, such as Parkinson?s disease, result in clinical movement disorders, or whether the basal ganglia might also be involved in such mental disorders, such as Attention Deficit Hyperactivity Disorder, or in the abuse of psychoactive drugs. Work done in this past year addressed primarily the second question. Current work is focused on extending our prior findings that dopamine, through the segregation of the D1 and D2 dopamine receptor subtypes in the """"""""direct"""""""" and """"""""indirect"""""""" striatal output neurons, regulates the balanced function of striatal output pathways. Neuromodulators such as dopamine act to alter the long term response of neurons to synaptic input, such as the glutamatergic excitatory input from the cortex. Such neuroplasticity is mediated by the activation of neurotransmitter receptor-mediated activation of protein kinase signal transduction pathways, which result in the activation of transcription factors and induction of specific genes that are responsible for altering synaptic responses. We demonstrated that in the striatum, the ?direct? and ?indirect? striatal projection neurons support distinct forms of neuronal plasticity that affect responses to cortical input, through the differential activation of distinct protein kinase signaling pathways, and dopamine maintains these different forms of response. Dysfunction of the striatum following dopamine lesions in animal models of Parkinson?s disease, appear to be due to a particularly aberrant form of neuronal plasticity that is due to a switch in the regulation of a particular protein kinase signal transduction pathway.
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