GABAergic neurotransmission in globus pallidus and its involvement in neurologic disorders

Abstract

The globus pallidus occupies a critical position in the 'indirect' pathway of the basal ganglia and, as such, plays an important role in the modulation of movement. In recent years, the importance of the globus pallidus in the normal and malfunctioned basal ganglia is emerging. However, the function and operation of various transmitter systems in this nucleus are largely unknown. GABA is the major neurotransmitter involved in the globus pallidus. By means of electrophysiological recording, immunohistochemistry and behavioral studies, new information on the distribution and functions of the GABAergic neurotransmission in the rat globus pallidus has been generated. Morphological studies revealed the existence of GABA(A) receptor, including its benzodiazepine binding site, and GABA(B) receptor in globus pallidus. At subcellular level, GABA(A) receptors are located at the postsynaptic sites of symmetric synapses (putative GABAergic synapses). However, GABA(B) receptors are located at both pre- and postsynaptic sites of symmetric, as well as asymmetric synapses (putative excitatory synapses). Consistent with the morphological results, functional studies showed that activation of GABA(B) receptors in globus pallidus reduces the release of GABA and glutamate by activating presynaptic auto- and heteroreceptors, and hyperpolarizes pallidal neurons by activating postsynaptic receptors. In addition to GABA(B) receptor, activation of GABA(A) receptor benzodiazepine binding site and blockade of GABA uptake change the activity of globus pallidus by prolonging the duration of GABA current. In agreement with the in vitro effect, activation of GABA(B) receptor, GABA(A) receptor benzodiazepine binding site and blockade of GABA uptake cause rotation in behaving animal. Furthermore, the GABA system in the globus pallidus is involved in the etiology of Parkinson's disease and regulation of seizures threshold. It has been demonstrated that the abnormal hypoactivity and synchronized rhythmic discharge of globus pallidus neurons associate with akinesia and resting tremor in parkinsonism. Recent electrophysiological and behavioral studies indicated that the new anti-epileptic drug, tiagabine, is functional in globus pallidus, which may present more information to understand the involvement of globus pallidus in epilepsy.