The University of Southampton
University of Southampton Institutional Repository

Dual effect of high frequency stimulation on subthalamic neuron activity

Dual effect of high frequency stimulation on subthalamic neuron activity
Dual effect of high frequency stimulation on subthalamic neuron activity
Although it is well known that high-frequency stimulation (HFS) of the subthalamic nucleus (STN) alleviates the cardinal symptoms of Parkinson's disease, the underlying mechanisms are not fully understood. We investigated the effect of stimulation from low to high frequencies on rat STN neurons in naive and dopamine-depleted slices using whole-cell, current-clamp techniques and on-line artifact suppression. Stimulation at 10 Hz evoked 10 Hz single spikes but did not significantly modify ongoing STN activity. In contrast, at therapeutically relevant frequencies (80-185 Hz), stimulation had a dual effect: it fully suppressed STN spontaneous activity and generated a robust pattern of recurrent bursts of spikes, with each spike being time-locked to a stimulus pulse. Neither the suppression of spontaneous activity nor the generation of spikes was prevented by the antagonists of the metabotropic and ionotropic receptors of glutamate and -aminobutyric acid. Tetrodotoxin, the Na+ channel blocker, suppressed all HFS-evoked spikes, whereas nifedipin, an L-type Ca2+-channel blocker, abolished the membrane oscillations underlying bursts. Therefore, we conclude that HFS drives the STN neuronal activity by directly activating the neuronal membrane. We suggest that this pattern may remove the deleterious activity of the basal ganglia network in the parkinsonian state and drive target neurons to a high-frequency state of activity, dependent on the characteristics of STN efferent synapses and resonant properties of target membranes.
high-frequency stimulation, subthalamic nucleus, evoked bursting state, patch-clamp recordings, in vitro, gamma band frequency
8743-8751
Garcia, Liliana
c9c42bae-f632-44b5-ba0d-7ddc8399fc54
Audin, Jacques
284ffc2b-7011-4dc0-a9b7-e7906cd7e45b
D'Alessandro, Giampaolo
bad097e1-9506-4b6e-aa56-3e67a526e83b
Bioulac, Bernard
a0fe511b-6de8-4cb6-9395-27bd81f2f904
Hammond, Constance
9e3ccab2-6aab-4200-89b3-77ec86e08c71
Garcia, Liliana
c9c42bae-f632-44b5-ba0d-7ddc8399fc54
Audin, Jacques
284ffc2b-7011-4dc0-a9b7-e7906cd7e45b
D'Alessandro, Giampaolo
bad097e1-9506-4b6e-aa56-3e67a526e83b
Bioulac, Bernard
a0fe511b-6de8-4cb6-9395-27bd81f2f904
Hammond, Constance
9e3ccab2-6aab-4200-89b3-77ec86e08c71

Garcia, Liliana, Audin, Jacques, D'Alessandro, Giampaolo, Bioulac, Bernard and Hammond, Constance (2003) Dual effect of high frequency stimulation on subthalamic neuron activity. Journal of Neuroscience, 23 (25), 8743-8751.

Record type: Article

Abstract

Although it is well known that high-frequency stimulation (HFS) of the subthalamic nucleus (STN) alleviates the cardinal symptoms of Parkinson's disease, the underlying mechanisms are not fully understood. We investigated the effect of stimulation from low to high frequencies on rat STN neurons in naive and dopamine-depleted slices using whole-cell, current-clamp techniques and on-line artifact suppression. Stimulation at 10 Hz evoked 10 Hz single spikes but did not significantly modify ongoing STN activity. In contrast, at therapeutically relevant frequencies (80-185 Hz), stimulation had a dual effect: it fully suppressed STN spontaneous activity and generated a robust pattern of recurrent bursts of spikes, with each spike being time-locked to a stimulus pulse. Neither the suppression of spontaneous activity nor the generation of spikes was prevented by the antagonists of the metabotropic and ionotropic receptors of glutamate and -aminobutyric acid. Tetrodotoxin, the Na+ channel blocker, suppressed all HFS-evoked spikes, whereas nifedipin, an L-type Ca2+-channel blocker, abolished the membrane oscillations underlying bursts. Therefore, we conclude that HFS drives the STN neuronal activity by directly activating the neuronal membrane. We suggest that this pattern may remove the deleterious activity of the basal ganglia network in the parkinsonian state and drive target neurons to a high-frequency state of activity, dependent on the characteristics of STN efferent synapses and resonant properties of target membranes.

Text
8743.pdf - Version of Record
Restricted to Repository staff only
Request a copy

More information

Published date: September 2003
Keywords: high-frequency stimulation, subthalamic nucleus, evoked bursting state, patch-clamp recordings, in vitro, gamma band frequency

Identifiers

Local EPrints ID: 29307
URI: http://eprints.soton.ac.uk/id/eprint/29307
PURE UUID: f550e850-7ad2-41ea-be2a-c148336b4d07
ORCID for Giampaolo D'Alessandro: ORCID iD orcid.org/0000-0001-9166-9356

Catalogue record

Date deposited: 11 May 2006
Last modified: 10 Jan 2022 02:37

Export record

Contributors

Author: Liliana Garcia
Author: Jacques Audin
Author: Bernard Bioulac
Author: Constance Hammond

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×