Short-Term Plasticity Shapes the Response to Simulated Normal and Parkinsonian Input Patterns in the Globus Pallidus

Abstract

Basal ganglia structures show strong activity modulation during movement and synchronous bursting in Parkinson's disease. Recent work has shown that short-term synaptic plasticity (STP) can play an important role in the effect of temporal activity patterns on postsynaptic targets. To determine the role of STP in the subthalamic nucleus (STN) to globus pallidus (GP) connection, which has been suggested to underlie rhythmical bursting in Parkinson's disease, we first measured STP using trains of electrical input stimulation in vitro. We found that STN inputs to GP typically show both facilitation and depression with input frequencies of 10-100 Hz and that facilitation is dominant for the first few inputs in a train but that depression takes over subsequently. We quantified the strength and time course of facilitation and depression using a computational model of STP. Using the STP model, we constructed synaptic conductance patterns of normal and Parkinsonian STN activity and applied these conductances to GP neurons in vitro using the technique of dynamic clamping. We show that STP controls the slope and shape of the function describing the steady-state level of GP neuron firing in response to different levels of STN input. In addition, we show that STP modulates responses of GP neurons to bursts and pauses in the input pattern. These findings indicate that STP plays an important role in modulating both spike rates and temporal patterns of GP activity in the normal state, as well as in Parkinson's disease.