Channel density distributions explain spiking variability in the globus pallidus: A combined physiology and computer simulation database approach

• Type of Material: Article
• Authors: Cengiz Guenay, Emory University; Jeremy R. Edgerton, Emory University; Dieter Jaeger, Emory University
• Language: English
• Date: 2008-07-23
• Publisher: Society for Neuroscience
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2008 Society for Neuroscience.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.4198-07.2008
• Title of Journal or Parent Work: Journal of Neuroscience
• Volume: 28
• Issue: 30
• Start Page: 7476
• End Page: 7491
• Grant/Funding Information: This work was supported by National Institute of Neurological Disorders and Stroke Grant R01-NS039852 and National Institute of Mental Health Grant R01-MH065634.
• Keywords: PERSISTENT SODIUM CURRENT; Neurosciences & Neurology; in vitro; ACTION-POTENTIAL INITIATION; PYRAMIDAL NEURONS; POTASSIUM CHANNELS; SUBTHALAMIC NUCLEUS; RECEPTOR ACTIVATION; Life Sciences & Biomedicine; excitability; NIGRA PARS RETICULATA; Neurosciences; NEURONS IN-VITRO; ion channel; neuron; basal ganglia; model; BASAL GANGLIA; ACTIVITY-DEPENDENT REGULATION; Science & Technology
• Research Categories: Biology, Neuroscience

Abstract

Globus pallidus (GP) neurons recorded in brain slices show significant variability in intrinsic electrophysiological properties. To investigate how this variability arises, we manipulated the biophysical properties of GP neurons using computer simulations. Specifically, we created a GP neuron model database with 100,602 models that had varying densities of nine membrane conductances centered on a hand-tuned model that replicated typical physiological data. To test the hypothesis that the experimentally observed variability can be attributed to variations in conductance densities, we compared our model database results to a physiology database of 146 slice recordings. The electrophysiological properties of generated models and recordings were assessed with identical current injection protocols and analyzed with a uniform set of measures, allowing a systematic analysis of the effects of varying voltage-gated and calcium-gated conductance densities on the measured properties and a detailed comparison between models and recordings. Our results indicated that most of the experimental variability could be matched by varying conductance densities, which we confirmed with additional partial block experiments. Further analysis resulted in two key observations: (1) each voltage-gated conductance had effects on multiple measures such as action potential waveform and spontaneous or stimulated spike rates; and (2) the effect of each conductance was highly dependent on the background context of other conductances present. In some cases, such interactions could reverse the effect of the density of one conductance on important excitability measures. This context dependence of conductance density effects is important to understand drug and neuromodulator effects that work by affecting ion channels.