Neurotransmitter release from high-frequency stimulation of the subthalamic nucleus

Lee, Kendall H.; Su, Chang; Roberts, David W.; Kim, Uhnoh

doi:10.3171/jns.2004.101.3.0511

Cited by 145 publications

(100 citation statements)

References 51 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The early finding that DBS of the STN or GPi results in clinical benefits that are strikingly similar to those of lesioning at these sites for tremor and PD, respectively, suggested initially that DBS may act by inhibiting neurons in the area of stimulation [269][270][271]. This view was supported by the demonstration that some neurons in the vicinity of the stimulation site in STN and GPi in experimental animals and in patients with PD are, indeed, inhibited [272][273][274][275], perhaps by depolarization block or the release of GABA from terminals of afferents to the stimulated area [276][277][278][279][280].…”

Section: Dbs Mechanism Of Actionmentioning

confidence: 83%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

View full text Add to dashboard Cite

Deep brain stimulation (DBS) is highly effective for both hypo-and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal gangliathalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

show abstract

Section: Dbs Mechanism Of Actionmentioning

confidence: 83%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

View full text Add to dashboard Cite

show abstract

“…24 Perhaps reflecting this stimulatory effect, the activity of dopaminergic neurons increases in the substantia nigra compacta during HFS of the STN. 16 Moreover, neurotransmitter levels rise within the basal ganglia during HFS of the STN: dopamine levels rise in the striatum, 15 g-aminobutyric acid increases in the globus pallidus interna, 38 and glutamate levels increase within the STN 17 and globus pallidus interna. 38,39 The similarities between the effects of surgical lesions, which ought to eliminate neuronal activity, and the effects of DBS on the symptoms of PD are hard to reconcile with evidence of persistent neuronal activity and increased neurotransmitter levels in the basal ganglia during DBS.…”

Section: Suppression Of Alcohol Intake By Dbs In P Ratsmentioning

confidence: 99%

Deep brain stimulation of the nucleus accumbens reduces alcohol intake in alcohol-preferring rats

Henderson

Green

Bradford³

et al. 2010

FOC

Self Cite

106

View full text Add to dashboard Cite

Object The authors tested the hypothesis that deep brain stimulation (DBS) in the nucleus accumbens (NAcc) decreases alcohol intake in alcohol-preferring (P) rats after each animal has established a stable, large alcohol intake and after P rats with an established intake have been deprived of alcohol for 4–6 weeks. Methods Bipolar stimulating electrodes were bilaterally placed in the NAcc using stereotactic coordinates. In the first study, P rats (9 animals) were allowed to establish a stable pattern of alcohol intake (about 5–7 g/day) over approximately 2 weeks, and the acute effects of DBS in the NAcc (140–150 Hz, 60-μsec pulse width, and 200-μA current intensity) on alcohol intake and alcohol preference were studied. Each animal acted as its own control and received 1 hour of DBS followed by 1 hour of sham-DBS or vice versa on each of 2 sequential days. The order of testing (sham-DBS vs DBS) was randomized. In the second study, each animal was allowed to establish a stable alcohol intake and then the animal was deprived of alcohol for 4–6 weeks. Animals received DBS (6 rats) or sham-DBS (5 rats) in the NAcc for 24 hours starting when alcohol was reintroduced to each animal. Results Deep brain stimulation in the NAcc, as compared with a period of sham-DBS treatment in the same animals, acutely decreased alcohol preference. Furthermore, alcohol consumption and preference were significantly reduced in the DBS group compared with the sham treatment group during the first 24 hours that alcohol was made available after a period of forced abstinence. Conclusions The NAcc plays a key role in the rewarding and subsequent addictive properties of drugs of abuse in general and of alcohol in particular. Deep brain stimulation in the NAcc reduced alcohol consumption in P rats both acutely and after a period of alcohol deprivation. Therefore, DBS in the NAcc coupled with other neurophysiological measurements may be a useful tool in determining the role of the NAcc in the mesocorticolimbic reward circuit. Deep brain stimulation in the NAcc may also be an effective treatment for reducing alcohol consumption in patients who abuse alcohol and have not responded to other forms of therapy.

show abstract

“…However, it is not known whether HFS acts to modulate potassium dynamics through (i) voltage gated conductances (influx, efflux) or (ii) uptake via electrogenic pumps. The literature indicates that although glutamate release is enhanced during pulse train HFS (Lee et al 2004), electrogenic pumps are not adversely affected, maintaining glutamate and potassium clearance during stimulation (Diamond & Jahr 2000).…”

Section: Role Of Potassium Diffusion In Axon Bundlesmentioning

confidence: 99%

Potassium diffusive coupling in neural networks

Durand

Park

Jensen

2010

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

Conventional neural networks are characterized by many neurons coupled together through synapses. The activity, synchronization, plasticity and excitability of the network are then controlled by its synaptic connectivity. Neurons are surrounded by an extracellular space whereby fluctuations in specific ionic concentration can modulate neuronal excitability. Extracellular concentrations of potassium ([K þ ] o ) can generate neuronal hyperexcitability. Yet, after many years of research, it is still unknown whether an elevation of potassium is the cause or the result of the generation, propagation and synchronization of epileptiform activity. An elevation of potassium in neural tissue can be characterized by dispersion (global elevation of potassium) and lateral diffusion (local spatial gradients). Both experimental and computational studies have shown that lateral diffusion is involved in the generation and the propagation of neural activity in diffusively coupled networks. Therefore, diffusion-based coupling by potassium can play an important role in neural networks and it is reviewed in four sections. Section 2 shows that potassium diffusion is responsible for the synchronization of activity across a mechanical cut in the tissue. A computer model of diffusive coupling shows that potassium diffusion can mediate communication between cells and generate abnormal and/or periodic activity in small ( §3) and in large networks of cells ( §4). Finally, in §5, a study of the role of extracellular potassium in the propagation of axonal signals shows that elevated potassium concentration can block the propagation of neural activity in axonal pathways. Taken together, these results indicate that potassium accumulation and diffusion can interfere with normal activity and generate abnormal activity in neural networks.

show abstract

Neurotransmitter release from high-frequency stimulation of the subthalamic nucleus

Abstract: During HFS of STN neurons the mechanism of DBS may involve the release of neurotransmitters rather than the primary electrogenic inhibition of neurons.

Cited by 145 publications

References 51 publications

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

Deep brain stimulation of the nucleus accumbens reduces alcohol intake in alcohol-preferring rats

Potassium diffusive coupling in neural networks

Contact Info

Product

Resources

About