GAT-3 Dysfunction Generates Tonic Inhibition in Exter nal Globus Pallidus Neurons in Parkinsonian Rodents
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...
| Authors: | , , , , , , , , , , |
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| Format: | article |
| Publication Date: | 2018 |
| Country: | España |
| Institution: | Universidad del País Vasco |
| Repository: | Addi. Archivo Digital para la Docencia y la Investigación |
| OAI Identifier: | oai:addi.ehu.eus:10810/29869 |
| Online Access: | http://hdl.handle.net/10810/29869 |
| Access Level: | Open access |
| Keyword: | extrasynaptic gaba(a) receptors monkey basal ganglia synaptic-transmission subthalamic nucleus projection neurons transporter gat-1 beta oscillations adult-rat in-vitro plasticity |
| Summary: | 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 down-regulated 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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