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The Journal of Neurophysiology Vol. 87 No. 3 March 2002, pp. 1348-1362
Copyright ©2002 by the American Physiological Society
1Department of Anatomy and Neurobiology, University of Tennessee, Memphis, Tennessee 38163; 2University of Oxford, Medical Research Council Anatomical Neuropharmacology Unit, Oxford OX1 3TH, United Kingdom; and 3Division of Life Science, University of Texas, San Antonio, Texas 78294
Bevan, M. D.,
P. J. Magill,
N. E. Hallworth,
J. P. Bolam, and
C. J. Wilson.
Regulation of the Timing and Pattern of Action Potential
Generation in Rat Subthalamic Neurons In Vitro by GABA-A IPSPs. J. Neurophysiol. 87: 1348-1362, 2002. The
regulation of activity in the subthalamic nucleus (STN) by GABAergic
inhibition from the reciprocally connected globus pallidus (GP) plays
an important role in normal movement and disorders of movement. To
determine the precise manner in which GABAergic synaptic input, acting
at A-type receptors, influences the firing of STN neurons, we recorded
the response of STN neurons to GABA-A inhibitory postsynaptic
potentials (IPSPs) that were evoked by supramaximal electrical
stimulation of the internal capsule using the perforated-patch
technique in slices at 37°C. The mean equilibrium potential of the
GABA-A IPSP (EGABA-A IPSP) was 
79.4 ± 7.0 mV. Single IPSPs
disrupted the spontaneous oscillation that underlies rhythmic
single-spike firing in STN neurons. As the magnitude of IPSPs
increased, the effectiveness of prolonging the interspike interval was
related more strongly to the phase of the oscillation at which the IPSP
was evoked. Thus the largest IPSPs tended to reset the oscillatory
cycle, whereas the smallest IPSPs tended to produce relatively
phase-independent delays in firing. Multiple IPSPs were evoked at
various frequencies and over different periods and their impact was
studied on STN neurons held at different levels of polarization.
Multiple IPSPs reduced and/or prevented action potential generation
and/or produced sufficient hyperpolarization to activate a rebound
depolarization, which generated a single spike or restored rhythmic
spiking and/or generated a burst of activity. The pattern of IPSPs and
the level of polarization of STN neurons were critical in determining
the nature of the response. The duration of bursts varied from 20 ms to
several hundred milliseconds, depending on the intrinsic rebound
properties of the postsynaptic neuron. These data demonstrate that
inhibitory input from the GP can produce a range of firing patterns in
STN neurons, depending on the number and frequencies of IPSPs and the
membrane properties and voltage of the postsynaptic neuron.
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