AI Article Synopsis
- The external globus pallidus (GP) plays a crucial role in motor control by acting as a GABAergic hub in the basal ganglia circuitry, which is affected in Parkinson's disease (PD).
- In rodent models of PD, GP neuron activity is disrupted and there's a significant increase in extracellular GABA levels, indicating changes in how GABA is processed in the brain.
- The study reveals that in dopamine-depleted rodents, there is persistent GABAergic tonic inhibition in GP neurons due to downregulated glial GAT-3 transporters, suggesting that this disruption contributes to motor coordination issues related to PD.
Article Abstract
The external globus pallidus (GP) is a key GABAergic hub in the basal ganglia (BG) circuitry, a neuronal network involved in motor control. In Parkinson's disease (PD), the rate and pattern of activity of GP neurons are profoundly altered and contribute to the motor symptoms of the disease. In rodent models of PD, the striato-pallidal pathway is hyperactive, and extracellular GABA concentrations are abnormally elevated in the GP, supporting the hypothesis of an alteration of neuronal and/or glial clearance of GABA. Here, we discovered the existence of persistent GABAergic tonic inhibition in GP neurons of dopamine-depleted (DD) rodent models. We showed that glial GAT-3 transporters are downregulated while neuronal GAT-1 function remains normal in DD rodents. Finally, we showed that blocking GAT-3 activity in vivo alters the motor coordination of control rodents, suggesting that GABAergic tonic inhibition in the GP contributes to the pathophysiology of PD.
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| http://dx.doi.org/10.1016/j.celrep.2018.04.014 | DOI Listing |
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