Influence Of Gabazine On Firing Activity Of Pallidal Neurons In Mice

The globus pallidus occupies an important position in the indirect pathway of the basal ganglia, and it plays an important role in normal movement regulation and in basal ganglia movement disorders. The globus pallidus mainly receives gamma-aminobutyric acid (GABA)ergic inputs from the striatum and local axon collaterals. GABA is the major inhibitory neurotransmitter used in the basal ganglia. A line of evidence indicated that there is a close relationship between GABA or GABAA receptors and Parkinson's disease. Early study revealed that microinjection of GABAA receptor antagonist, bicuculline, into the globus pallidus had marked antiparkinsonian effects. Therefore, it is very important to investigate the endogenous GABA transmitter system for understanding the function of globus pallidus under normal and pathologic state. Object:To investigate the electrophysiological effects of endogenous GABAA receptor in the globus pallidus of normal and MPTP parkinsonian mice. Methods:The parkisonian mice was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In vivo extracellular recording was used to detect the effects of GABAA receptor antagonist, gabazine, on spontaneous firing rate of pallidal neurons in normal and pakinsonian mice. Results:1. In normal mice, micro-pressure ejection of gabazine increased the spontaneous firing rate of pallidal neurons from 7.2±1.4 Hz to 10.4±1.8 Hz (P<0.001). The average increase was 53.7±8.0%, which was significantly different (P<0.001) from that of vehicle (normal saline) injection.2. In MPTP treated mice, micro-pressure ejection of gabazine increased the spontaneous firing rate of pallidal neurons from 5.3±2.2 Hz to 6.8±2.7 Hz (P<0.01). The average increase was 42.9±7.5%, which was significantly different (P<0.001) from that of normal saline injection (P<0.001). Gabazine-induced increase in firing rate of globus pallidus had no significant difference in normal and MPTP treated parkinsonian mice.Conclusion:Gabazine increased the firing rate of globus pallidus neurons in normal and MPTP treated parkinsonian mice. The present findings may provide theoretical foundation for further investigations into the potential of pallidal endogenous GABAA receptor in treating Parkinson's disease.