Dynamic and spatial features of the inhibitory pallidal GABAergic synapses

The globus pallidus, one of the basal ganglia nuclei, plays a major role in both basal ganglia physiology and pathophysiology. The globus pallidus is innervated mainly by striatal spiny neurons and globus pallidus collaterals. These GABAergic synapses constitute 90% of the input to globus pallidus cells. Despite the dominance of this inhibitory GABAergic input, globus pallidus cells are spontaneously active and most of them increase their firing rate in a task related manner. To explain this apparent inconsistency, we studied the dynamic and spatial effects of GABAergic inputs to globus pallidus neurons. To this end, we used intra-cellular recording from globus pallidus neurons in rat brain slices, investigating the effect of bath and local GABA application, as well as the responses to electrical stimulation of the striatum. We showed that the properties of the responses to either local or global GABA applications are similar to the responses of globus pallidus cells to GABA release from nerve terminals. Since the stimulus-evoked responses have been shown to be inhibitory in nature, we concluded that GABAergic inputs to globus pallidus both at soma and dendrite level are inhibitory. Furthermore, we showed that GABA can promote globus pallidus synchronization by affecting the timing of globus pallidus spiking, and that the globus pallidus GABAergic synapse undergoes rapid frequency-dependent depression. This prominent synaptic depression can account for the ability of globus pallidus neurons to fire in the presence of a majority of inhibitory inputs and might indicate that globus pallidus neurons are tuned to detect frequency changes. Furthermore, globus pallidus synaptic depression rules out the possibility of activation of GABAeregic afferents as the main mechanisms of high-frequency deep brain stimulation, used for treatment of severe parkinsonian patients.