Intrapallidal injection of 6-hydroxydopamine induced changes in dopamine innervation and neuronal activity of globus pallidus

Abstract

The globus pallidus (GP) plays an important role in basal ganglia circuitry. In contrast to the well-characterized actions of dopamine on striatal neurons, the functional role of the dopamine innervation of GP is still not clearly determined. The present study aimed to investigate the effects of intrapallidal injection of 6-hydroxydopamine (6-OHDA) on rotational behavior induced by apomorphine, on the loss of dopamine cell bodies in the substantia nigra pars compacta (SNc) and fibers in the GP and striatum and on in vivo extracellularly-recorded GP neurons in the rat. Injection of 6-OHDA into GP induced severe loss of tyrosine hydroxylase–immunoreactive (TH-IR) fibers in GP (−85%) with a reduction in the number of TH-IR cell bodies in the SNc (−52%) and fibers in the striatum (−50%). S.c. injection of apomorphine in these rats induced a moderate number of turns (26±6 turns/5 min). Electrophysiological recordings show that 6-OHDA injection in GP induced a significant decrease of the firing rate of GP neurons (16.02±1.11 versus 24.14±1.58 spikes/sec in control animals and 22.83±1.28 in sham animals, one-way ANOVA , P<0.0001) without any change in the firing pattern (χ 2=1.03, df=4, P=0.90). Our results support the premise of the existence of collaterals of SNc dopaminergic axons projecting to the striatum and GP and that dopamine plays a role in the modulation of the firing rate but not the firing pattern of GP neurons. Our data provide important insights into the functional role of the SNc–GP dopaminergic pathway suggesting that dopamine depletion in GP may participate in the development of motor disabilities.