Enhancement of excitatory synaptic integration by GABAergic inhibition in the subthalamic nucleus
Journal of Neuroscience. 2005-09-14; 25(37): 8505-8517
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1. J Neurosci. 2005 Sep 14;25(37):8505-17.
Enhancement of excitatory synaptic integration by GABAergic inhibition in the
Baufreton J(1), Atherton JF, Surmeier DJ, Bevan MD.
(1)Department of Physiology, Feinberg School of Medicine, Northwestern
University, Chicago, Illinois 60611, USA.
The activity patterns of subthalamic nucleus (STN) neurons, which are intimately
related to normal movement and abnormal movement in Parkinson’s disease (PD), are
sculpted by feedback GABAergic inhibition from the reciprocally connected globus
pallidus (GP). To understand the principles underlying the integration of
GABAergic inputs, we used gramicidin-based patch-clamp recording of STN neurons
in rat brain slices. Voltage-dependent Na+ (Nav) channels actively truncated
synthetic IPSPs and were required for autonomous activity. In contrast,
hyperpolarization-activated cyclic nucleotide-gated and class 3 voltage-dependent
Ca2+ channels contributed minimally to the integration of single or low-frequency
trains of IPSPs and autonomous activity. Interestingly, IPSPs modified action
potentials (APs) in a manner that suggested IPSPs enhanced postsynaptic Nav
channel availability. This possibility was confirmed in acutely isolated STN
neurons using current-clamp recordings containing IPSPs as voltage-clamp
waveforms. Tetrodotoxin-sensitive subthreshold and spike-associated Na+ currents
declined during autonomous spiking but were indeed transiently boosted after
IPSPs. A functional consequence of inhibition-dependent augmentation of
postsynaptic excitability was that EPSP-AP coupling was dramatically improved
when IPSPs preceded EPSPs. Because STN neuronal activity exhibits coherence with
cortical beta-oscillations in PD, we tested how rhythmic sequences of cortical
EPSPs were integrated in the absence and presence of feedback inhibition. STN
neuronal activity was consistently entrained by EPSPs only in the presence of
feedback inhibition. These observations suggest that feedback inhibition from the
GP is critical for the emergence of coherent beta-oscillations between the cortex
and STN in PD.
PMID: 16162932 [Indexed for MEDLINE]