Sodium Channels and Dendritic Spike Initiation at Excitatory Synapses in Globus Pallidus Neurons

• Type of Material: Article
• Authors: Jesse E. Hanson, Emory University; Yoland Smith, Emory University; Dieter Jaeger, Emory University
• Language: English
• Date: 2004-01-14
• Publisher: Society for Neuroscience
• Publication Version: Final Published Version
• Copyright Statement: © 2004 Society for Neuroscience 0270-6474/04/24329-12.00/0
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1523/JNEUROSCI.3937-03.2004
• Title of Journal or Parent Work: The Journal of Neuroscience
• Volume: 24
• Issue: 2
• Start Page: 329
• End Page: 340
• Grant/Funding Agency: National Institutes of Health
• Grant/Funding Information: This work was supported by National Institutes of Health Grants NS39852, RR00165, and MH12999.
• Keywords: globus pallidus; subthalamic nucleus; dendritic processing; synaptic integration; subcellular localization; sodium channel
• Subject - Topics: Synaptic physiology; Cellular neuroscience; Systems neuroscience

Abstract

Glutamatergic inputs from the subthalamic nucleus are suspected to provide a prominent source of excitation to globus pallidus (GP) neurons, despite their scarce number and mainly distal dendritic location. In this study we address the issue of whether dendritic sodium channels may facilitate the effect of excitatory inputs in GP. First, we examined the subcellular distribution of sodium channels using electron microscopic observations of immunoperoxidase and immunogold labeling. Voltage-gated sodium channels were found throughout GP dendrites and furthermore exhibited a specific clustering at sites of excitatory synaptic inputs. To examine the possibility that these channels could mediate dendritic spike generation, synaptic stimulation at visualized dendritic sites was performed during whole-cell recordings in vitro. These recordings revealed dendritic spike initiation in response to small excitatory inputs even for very distal stimulation sites. In contrast, subthreshold responses were mostly or fully attenuated at the soma for stimulation sites on distal dendrites. Computer simulations support the hypothesis that postsynaptic clustering of sodium channels allows dendritic triggering of spikes in response to inputs that would be too small to trigger a spike given uniformly distributed dendritic sodium channels. These findings indicate that postsynaptic sodium channel clustering is an effective mechanism to mediate a novel form of synaptic amplification and dendritic spike initiation. The ability of small amounts of excitation to trigger spikes in GP dendrites supports the prominent role of subthalamic input in the control of GP activity.