J Neural Transm [P-D Sect] (1995) 10:41-54 Journal of Neural Transmission 9 Springer-Verlag 1995 Printed in Austria Determinants of neuronal firing pattern in the guinea-pig subthalamic nucleus: an in vivo and in vitro comparison P. G. Overton* and S. A. Greenfield University Department of Pharmacology, Oxford, United Kingdom Accepted May 24, 1995 Summary. To ascertain the extent to which neuronal firing pattern in the subthalamic nucleus (STN) is determined by afferent inputs, a comparison was made between STN neurons recorded in vivo and in vitro (a largely denervated preparation). In vivo, the majority of cells exhibited an irregular firing pattern, although some showed evidence of burst firing. In contrast, all cells had a regular firing pattern in vitro. Electrical stimulation of the striatopallidal complex in vivo induced a short latency inhibition in STN neurons, followed by a burst of spikes. These effects could be reproduced in vitro; hyperpolarising pulses gave rist to a slow depolarising potential upon termination, which was accompanied by a burst of action potentials. Hence, the evidence suggests that afferents play an important role in determining the firing pattern of STN neurons. However, the cells also possess intrinsic membrane properties which allow inputs to trigger either single spikes or bursts. Keywords: Extracellular recording, intracellular recording, electrical stimula- tion, striatopallidal complex, burst firing. Introduction The subthalamic nucleus (STN) occupies a central position in current descriptions of basal ganglia function and dysfunction (Mitchell, 1991). How- ever, to date, the structure has attracted few electrophysiological investiga- tions. In particular, the degree to which neuronal firing pattern is under the control of afferent inputs or intrinsic membrane properties is uncertain. Firing pattern is an important parameter since alterations in pattern, especially discontinuous changes in firing rate (i.e. bursts) can lead to supra-additive increases in transmitter release (Gonon, 1988) and the preferential release of * Present address: Department of Psychology, University of Wales, Swansea, Single- ton Park, Swansea SA2 8PP, United Kingdom