Enhanced Ih Depresses Rat Entopeduncular Nucleus Neuronal Activity From High-Frequency Stimulation or Raised Ke+

High-frequency stimulation (HFS) is used to treat a variety of neurological diseases, yet its underlying therapeutic action is not fully elucidated. Previously, we reported that HFS-induced elevation in [K+]e or bath perfusion of raised Ke+ depressed rat entopeduncular nucleus (EP) neuronal activity via an enhancement of an ionic conductance leading to marked depolarization. Herein, we show that the hyperpolarization-activated ( Ih) channel mediates the HFS- or K+-induced depression of EP neuronal activity. The perfusion of an Ih channel inhibitor, 50 μM ZD7288 or 2 mM CsCl, increased input resistance by 23.5 ± 7% (ZD7288) or 35 ± 10% (CsCl), hyperpolarized cells by 3.4 ± 1.7 mV (ZD7288) or 2.3 ± 0.9 mV (CsCl), and decreased spontaneous action potential (AP) frequency by 51.5 ± 12.5% (ZD7288) or 80 ± 13.5% (CsCl). The Ih sag was absent with either treatment, suggesting a block of Ih channel activity. Inhibition of the Ih channel prior to HFS or 6 mM K+ perfusion not only prevented the previously observed decrease in AP frequency, but increased neuronal activity. Under voltage-clamp conditions, Ih currents were enhanced in the presence of 6 mM K+. Calcium is also involved in the depression of EP neuronal activity, since its removal during raised Ke+ application prevented this attenuation and blocked the Ih sag. We conclude that the enhancement of Ih channel activity initiates the HFS- and K+-induced depression of EP neuronal activity. This mechanism could underlie the inhibitory effects of HFS used in deep brain stimulation in output basal ganglia nuclei.

Download Full-text

High frequency stimulation or elevated K+ depresses neuronal activity in the rat entopeduncular nucleus

Neuroscience ◽

10.1016/j.neuroscience.2007.06.055 ◽

2007 ◽

Vol 149 (1) ◽

pp. 68-86 ◽

Cited By ~ 57

Author(s):

D.S. Shin ◽

M. Samoilova ◽

M. Cotic ◽

L. Zhang ◽

J.M. Brotchie ◽

...

Keyword(s):

Neuronal Activity ◽

High Frequency ◽

High Frequency Stimulation ◽

Entopeduncular Nucleus ◽

Frequency Stimulation

Download Full-text

Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy

Translational Psychiatry ◽

10.1038/tp.2011.5 ◽

2011 ◽

Vol 1 (5) ◽

pp. e5-e5 ◽

Cited By ~ 47

Author(s):

M-L Welter ◽

◽

P Burbaud ◽

S Fernandez-Vidal ◽

E Bardinet ◽

...

Keyword(s):

Basal Ganglia ◽

Neuronal Activity ◽

High Frequency ◽

High Frequency Stimulation ◽

Frequency Stimulation

Download Full-text

High-frequency stimulation of the entopeduncular nucleus improves dystonia in dtsz hamsters

Neuroreport ◽

10.1097/01.wnr.0000130435.75715.64 ◽

2004 ◽

Vol 15 (9) ◽

pp. 1391-1393 ◽

Cited By ~ 16

Author(s):

Daniel Harnack ◽

Melanie Hamann ◽

Wassilios Meissner ◽

Rudolf Morgenstern ◽

Andreas Kupsch ◽

...

Keyword(s):

High Frequency ◽

High Frequency Stimulation ◽

Entopeduncular Nucleus ◽

Frequency Stimulation ◽

Stimulation Of

Download Full-text

High-frequency stimulation of the subthalamic nucleus modulates neuronal activity in the lateral habenula nucleus

European Journal of Neuroscience ◽

10.1111/ejn.13397 ◽

2016 ◽

Vol 44 (9) ◽

pp. 2698-2707 ◽

Cited By ~ 7

Author(s):

Henrike Hartung ◽

Sonny K. H. Tan ◽

Yasin Temel ◽

Trevor Sharp

Keyword(s):

Subthalamic Nucleus ◽

Neuronal Activity ◽

High Frequency ◽

High Frequency Stimulation ◽

Lateral Habenula ◽

Frequency Stimulation ◽

Stimulation Of

Download Full-text

Electrophysiological and metabolic evidence that high‐frequency stimulation of the subthalamic nucleus bridles neuronal activity in the subthalamic nucleus and the substantia nigra reticulata

The FASEB Journal ◽

10.1096/fj.03-0163com ◽

2003 ◽

Vol 17 (13) ◽

pp. 1820-1830 ◽

Cited By ~ 173

Author(s):

Chun-Hwei Tai ◽

Thomas Boraud ◽

Erwan Bezard ◽

Bernard Bioulac ◽

Christian Gross ◽

...

Keyword(s):

Substantia Nigra ◽

Subthalamic Nucleus ◽

Neuronal Activity ◽

High Frequency ◽

High Frequency Stimulation ◽

Frequency Stimulation ◽

Substantia Nigra Reticulata ◽

Stimulation Of

Download Full-text

Subthalamic Stimulation and Neuronal Activity in the Substantia Nigra in Parkinson's Disease

Journal of Neurophysiology ◽

10.1152/jn.01104.2006 ◽

2007 ◽

Vol 97 (6) ◽

pp. 4017-4022 ◽

Cited By ~ 43

Author(s):

D. Maltête ◽

N. Jodoin ◽

C. Karachi ◽

J. L. Houeto ◽

S. Navarro ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Firing Rate ◽

Neuronal Activity ◽

High Frequency ◽

High Frequency Stimulation ◽

Motor Disability ◽

Frequency Stimulation ◽

The Mean

High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for severe forms of Parkinson's disease (PD). To study the effects of high-frequency STN stimulation on one of the main output pathways of the basal ganglia, single-unit recordings of the neuronal activity of the substantia nigra pars reticulata (SNr) were performed before, during, and after the application of STN electrical stimulation in eight PD patients. During STN stimulation at 14 Hz, no change in either the mean firing rate or the discharge pattern of SNr neurons was observed. STN stimulation at 140 Hz decreased the mean firing rate by 64% and the mean duration of bursting mode activity of SNr neurons by 70%. The SNr residual neuronal activity during 140-Hz STN stimulation was driven by the STN stimulation. How the decrease in rate and modification of firing pattern of SNr-evoked neural activity, during high-frequency STN stimulation, contribute to the improvement of parkinsonian motor disability remains to be elucidated.

Download Full-text

Alleviation of Tinnitus With High-Frequency Stimulation of the Dorsal Cochlear Nucleus: A Rodent Study

Trends in Hearing ◽

10.1177/2331216519835080 ◽

2019 ◽

Vol 23 ◽

pp. 233121651983508 ◽

Cited By ~ 2

Author(s):

Gusta van Zwieten ◽

Ali Jahanshahi ◽

Marlieke L. van Erp ◽

Yasin Temel ◽

Robert J. Stokroos ◽

...

Keyword(s):

Neuronal Activity ◽

Cochlear Nucleus ◽

High Frequency ◽

Auditory Pathway ◽

Dorsal Cochlear Nucleus ◽

High Frequency Stimulation ◽

Noise Trauma ◽

Frequency Stimulation ◽

Central Auditory Pathway ◽

Stimulation Of

Deep brain stimulation of the central auditory pathway is emerging as a promising treatment modality for tinnitus. Within this pathway, the dorsal cochlear nucleus (DCN) plays a key role in the pathophysiology of tinnitus and is believed to be a tinnitus generator. We hypothesized that high-frequency stimulation (HFS) of the DCN would influence tinnitus-related abnormal neuronal activity within the auditory pathway and hereby suppress tinnitus. To this end, we assessed the effect of HFS of the DCN in a noise-induced rat model of tinnitus. The presence of tinnitus was verified using the gap prepulse inhibition of the acoustic startle response paradigm. Hearing thresholds were determined before and after noise trauma by measuring the auditory brainstem responses. In addition, changes in neuronal activity induced by noise trauma and HFS were assessed using c-Fos immunohistochemistry in related structures. Results showed tinnitus development after noise trauma and hearing loss ipsilateral to the side exposed to noise trauma. During HFS of the DCN, tinnitus was suppressed. There was no change in c-Fos expression within the central auditory pathway after HFS. These findings suggest that DCN-HFS changes patterns of activity and results in information lesioning within the network and hereby blocking the relay of abnormal tinnitus-related neuronal activity.

Download Full-text

Frequency and vagal effects

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1961.200.4.715 ◽

1961 ◽

Vol 200 (4) ◽

pp. 715-717 ◽

Cited By ~ 1

Author(s):

Wei Young ◽

Frank Upham

Keyword(s):

High Frequency ◽

Vagal Stimulation ◽

Inhibitory Effect ◽

High Frequency Stimulation ◽

Inhibitory Effects ◽

Optimal Frequency ◽

Frequency Stimulation ◽

Heart Preparation ◽

Second Period ◽

Frequency Of Stimulation

Effects of frequency of stimulation were studied in the isolated vagal heart preparation of Rana pipiens. Normal inhibitory effects were readily obtainable by stimulating the vagus nerve at pulse rates between 10 pulses/sec. and 100 pulses/sec. for a period of 10 seconds. A little above 100 pulses/sec. or below 10 pulses/ sec. the heart was usually less responsive to the same period of vagal stimulation. Below 5 pulses/sec. or above 200 pulses/ sec. the isolated preparation was practically nonresponsive to vagal stimulation for the 10-second period. The heart was responsive to the lower pulse rate but not to the higher rate when stimulated for a longer period. Arrhythmia usually was induced by frequent application of high-frequency stimulation. This suggests that the pacemaker is somehow temporarily impaired by high-frequency bombardment. The inhibitory effect is proportional to the duration of the impulse for any optimal frequency. The observed inhibitory vagal phenomenon results primarily from the liberation of an acetylcholine-like substance from the vagal nerve endings. The amount of this substance liberated can be assayed quantitatively. It was estimated that each optimal volley liberated approximately 2.5 x 10–11 gm of acetylcholine-like substance.

Download Full-text

Depression of postsynaptic potentials by high-frequency stimulation in embryonic motoneurons grown in spinal cord slice cultures

Journal of Neurophysiology ◽

10.1152/jn.1992.68.5.1793 ◽

1992 ◽

Vol 68 (5) ◽

pp. 1793-1803 ◽

Cited By ~ 21

Author(s):

J. Streit ◽

C. Luscher ◽

H. R. Luscher

Keyword(s):

Spinal Cord ◽

Dorsal Root Ganglia ◽

High Frequency ◽

Dorsal Root ◽

Input Resistance ◽

Synaptic Depression ◽

High Frequency Stimulation ◽

Postsynaptic Potentials ◽

Wide Range ◽

Frequency Stimulation

1. In embryonic cocultures of spinal cord, dorsal root ganglia, and muscle, excitatory postsynaptic potentials (EPSPs) were recorded in motoneurons during focal electrical stimulation of the dorsal root ganglia or the spinal cord. 2. EPSPs were depressed in amplitude at high-frequency stimulation relative to a control frequency of 0.5 Hz by 47 and 75% at 5 and 10 Hz, respectively. This was true for composite EPSPs and unitary EPSPs. 3. The depression showed a wide range of variability between individual experiments. The degree of depression at 5 Hz was negatively correlated to the rate of spontaneous excitatory input the motoneurons received. There was no correlation to the soma size, the average amplitude of the EPSPs, the rheobase, or the input resistance of the motoneurons. 4. An increase in latency of EPSPs was observed concomitant with or preceding the synaptic depression in most experiments. Total transmission failures, which were absent at low-frequency stimulation, appeared during depression. 5. Large incremental steps in amplitude could be seen during depression, suggesting that several release sites were switched off and on together. 6. Decreasing the extracellular calcium concentration from 5 to 1 mM led to a decrease in the frequency sensitivity of the synaptic efficacy and to a decrease of the EPSP amplitude and latency. 7. Measurements of the antidromic conduction of action potentials evoked in the axons and recorded in the somata of dorsal root ganglion cells revealed an increase in latency and the appearance of conduction failures at stimulation frequencies of 1-10 Hz. The frequency modulation of conduction was decreased in 1 mM compared with 5 mM external calcium. 8. Together these findings suggest that conduction failures in the presynaptic axons contribute to the synaptic depression of EPSPs in embryonic motoneurons.

Download Full-text