Dopamine Modulates Corticostriatal Inputs During Motor Command Signalilng
type: CreativeWork
description: Normal motor signaling in the basal ganglia requires regulating which movements to suppress and which to enact. In Parkinson's disease, loss of dopamine levels due to loss of dopaminergic neurons results in unbalanced basal ganglia output and loss of motor control. Motor sequences are thought to be triggered by cortical inputs as these glutamatergic inputs provide the main excitatory drive to the striatal output neurons. Dopamine is a crucial modulator of corticostriatal activity and loss of its normal function plays an important role in the pathophysiology of Parkinson's disease. We hypothesize that the functional reorganization of the cortical inputs to the striatum following long-term dopamine depletion as well as the response to dopamine replacement therapies has important functional implications in the pathogenesis and treatment of Parkinson's disease motor symptoms. To address this hypothesis, we adapted an optical technique using lipophilic dye, FM 1-43, to characterize the activities of the two major classes of corticostriatal projection neurons - the ipsilateral and contralateral cortical projections - and compared the influence of dopamine D2 receptors on these inputs. We found that both cortical projections shared similar patterns of terminal release and were both inhibited by D2 receptor activation. A D2 receptor-mediated inhibition specifically targeted the least active (slow-releasing) corticostriatal inputs with low probability of release. This "filtering" effect by D2 receptors confirmed a role for dopamine in modulating excitatory cortical inputs that could be crucial to selection of proper motor functions. To study the loss of motor control during conditions of chronic dopamine depletion, we employed a classic Parkinson's disease rodent model in which dopamine is depleted from one hemisphere using the neurotoxin, 6-hydroxydopamine. Behavior tests confirmed lateralized motor response due to loss of function in the forelimb contralateral to the side …
abstract: Normal motor signaling in the basal ganglia requires regulating which movements to suppress and which to enact. In Parkinson's disease, loss of dopamine levels due to loss of dopaminergic neurons results in unbalanced basal ganglia output and loss of motor control. Motor sequences are thought to be triggered by cortical inputs as these glutamatergic inputs provide the main excitatory drive to the striatal output neurons. Dopamine is a crucial modulator of corticostriatal activity and loss of its normal function plays an important role in the pathophysiology of Parkinson's disease. We hypothesize that the functional reorganization of the cortical inputs to the striatum following long-term dopamine depletion as well as the response to dopamine replacement therapies has important functional implications in the pathogenesis and treatment of Parkinson's disease motor symptoms. To address this hypothesis, we adapted an optical technique using lipophilic dye, FM 1-43, to characterize the activities of the two major classes of corticostriatal projection neurons - the ipsilateral and contralateral cortical projections - and compared the influence of dopamine D2 receptors on these inputs. We found that both cortical projections shared similar patterns of terminal release and were both inhibited by D2 receptor activation. A D2 receptor-mediated inhibition specifically targeted the least active (slow-releasing) corticostriatal inputs with low probability of release. This "filtering" effect by D2 receptors confirmed a role for dopamine in modulating excitatory cortical inputs that could be crucial to selection of proper motor functions. To study the loss of motor control during conditions of chronic dopamine depletion, we employed a classic Parkinson's disease rodent model in which dopamine is depleted from one hemisphere using the neurotoxin, 6-hydroxydopamine. Behavior tests confirmed lateralized motor response due to loss of function in the forelimb contralateral to the side …
author: Wong, Minerva
language: English
keywords: Neurosciences
date published: 2013
date modified: 2026-07-24T01:44:27Z
provider: Columbia University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Columbia University

PropertyValue
property ID: DOI
value: 10.7916/D8HX1KXH