GABAA autoreceptors enhance GABA release from human neocortex: towards a mechanism for high-frequency stimulation (HFS) in brain?

Mantovani, M.; Möser, Andreas; Haas, Carola A.; Zentner, Josef; Feuerstein, Thomas J.

doi:10.1007/s00210-009-0410-3

Cited by 23 publications

(33 citation statements)

References 75 publications

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“…GABA may increase the firing rate of the GABAergic neuron through facilitatory somatodendritic GABA A autoreceptors. These GABA A autoreceptors have been demonstrated in human neocortical slices [17]. Whether these somatodendritic autoreceptors are facilitatory, like those on GABAergic terminals, or inhibitory, as usual for GABA A receptors, depends on the local somatodendritic chloride gradient.…”

Section: Diversity Of Effects Of Hfs In the Gp Medmentioning

confidence: 91%

“…The recently published findings of Mantovani et al [17] show that HFS of human neocortical slices selectively induces the release of GABA, involving facilitatory GABA A autoreceptors may serve as an in vitro backup for the proposed hypothesis of the mechanism of action of DBS-HFS. Note in this context that Mantovani et al excluded a release of glutamate.…”

Section: Hfs Applied In Parkinson`s Therapy Proposed Hypothesis: Hfsmentioning

confidence: 98%

“…GABA A receptor blockade, changing the plasmalemmal chloride gradient of GABA A receptor channels and tetrodotoxin (which abolishes action potentials) antagonized this HFS-evoked GABA release [17,37]. Thus, orthodromic action potentials may be induced in thalamopetal GABAergic axons by HFS within the GP med with subsequent release of GABA from their thalamic terminals; even more GABA release is due to activation by released GABA of facilitatory GABA A autoreceptors on these terminals.…”

Section: Diversity Of Effects Of Hfs In the Gp Medmentioning

confidence: 99%

“…in case of the PPN an augmentation of excitatory neuron activity, whereas HFS would abolish these effects, most likely through selective GABA release and activation of GABA A receptors on cholinergic and glutamatergic PPN neurons. Altoghether, this is an example for an in vivo correlation between HFS and GABA A receptor agonism (see [17] for an in vitro correlate). Note that PPN-LFS primarily leads to a melioration of the parkinsonian symptoms gait disturbance and postural instability, but rarely of other typical parkinsonian symptoms like rigidity or bradykinesia [23,26].…”

Section: Lfs Treatment Of Postural Imbalance and Gait Disturbancementioning

confidence: 99%

“…Whether these somatodendritic autoreceptors are facilitatory, like those on GABAergic terminals, or inhibitory, as usual for GABA A receptors, depends on the local somatodendritic chloride gradient. Using the pharmacological tool furosemide to change the plasmalemmal chloride gradient, Mantovani et al [17] did not differentiate between the involvement of somatodendritic and/or terminal autoreceptors in the mode of action of HFS. In any case, the overall effect of altering the chloride gradient was a decrease of HFSinduced GABA release.…”

Section: Diversity Of Effects Of Hfs In the Gp Medmentioning

confidence: 99%

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The mode of action of electrical high frequency stimulation

Kammerer¹,

Hebel²,

Feuerstein³

2010

JBiSE

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Section: Diversity Of Effects Of Hfs In the Gp Medmentioning

confidence: 91%

Section: Hfs Applied In Parkinson`s Therapy Proposed Hypothesis: Hfsmentioning

confidence: 98%

Section: Diversity Of Effects Of Hfs In the Gp Medmentioning

confidence: 99%

Section: Lfs Treatment Of Postural Imbalance and Gait Disturbancementioning

confidence: 99%

Section: Diversity Of Effects Of Hfs In the Gp Medmentioning

confidence: 99%

See 3 more Smart Citations

The mode of action of electrical high frequency stimulation

Kammerer¹,

Hebel²,

Feuerstein³

2010

JBiSE

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Effects of antiepileptic drugs on GABA release from rat and human neocortical synaptosomes

Kammerer

Rassner

Freiman

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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In epilepsy, allegedly, a neurotransmitter imbalance between the inhibitory GABA and the excitatory glutamate prevails. Therefore, some antiepileptic drugs (AEDs) are thought to increase GABA release. Because little is known about corresponding presynaptic effects of AEDs in the human brain, this study investigated the effects of carbamazepine, lamotrigine, phenytoin, gabapentin, pregabalin, levetiracetam, and valproate on (3)H-GABA release from human neocortical synaptosomes preincubated with (3)H-GABA. To obtain information on possible species differences, rat neocortical synaptosomes were investigated concomitantly. Release was evoked by either veratridine (1, 3.2, or 10 μM), which prevents activated voltage-dependent Na(+) channels from closing, or elevation of extracellular [K(+)] from 3 to 15 mM. The exocytosis inhibitor tetanus toxin (TeT) or withdrawal of buffer Ca(2+) (Ca (e) (2+) ) reduced K(+)-evoked release in both species, while blockade of Na(+) channels with tetrodotoxin had no effect. K(+)-evoked release was characterized as predominant, Ca(2+)-dependent and Na(+)-independent, exocytosis. Carbamazepine and phenytoin in the rat and carbamazepine, phenytoin, lamotrigine, and valproate in human tissue reduced K(+)-evoked (3)H-GABA release. With respect to veratridine-evoked release, Ca (e) (2+) withdrawal did not reduce release in the rat; it even increased the release in human tissue. TeT was slightly inhibitory in the rat. Blockade of GABA transport diminished veratridine-evoked (3)H-GABA release in either species. This release was characterized as mediated mainly by transporter reversal. Carbamazepine, lamotrigine, and phenytoin in rat tissue and carbamazepine and phenytoin in human decreased veratridine-induced (3)H-GABA release. Interestingly, no AED increased (3)H-GABA release. The reduction by AEDs of veratridine-evoked release was more intense than that of K(+)-evoked release. In conclusion, reduction of GABA release by AEDs may be the actual objective in a pathologically altered neuronal network where GABA acts in a depolarizing fashion.

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Selective GABA release as a mechanistic basis of high-frequency stimulation used for the treatment of neuropsychiatric diseases

Feuerstein

Kammerer

Lücking

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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Electrical high-frequency stimulation (HFS) is applied in many brain areas to treat various clinical syndromes. The nearly identical constellation of stimulation parameters raises the question of a unique mechanism of action of this therapeutic option. The identification of a single HFS mechanism may help to optimize the HFS technology by targeting this single mechanism. Experimentally, only axonal membranes are targets of HFS, but not other membranes of neurons or glial cells. Within all HFS target regions, axons of excitatory glutamatergic and inhibitory GABAergic neurons are present and play roles in all clinical syndromes treated successfully with HFS. Therefore, glutamatergic or GABAergic fibres are likely candidates as mediators of a unique HFS mode of action. The selective involvement of another neuronal fibre type (e.g. monoaminergic, cholinergic, etc.) in the HFS mode of action is highly unlikely since the regional and syndromal dissimilarity of the clinical HFS applications precludes the assumption of such a fibre type as primary HFS site of action. Our recent experimental finding that HFS of human neocortical slices induces the action potential-mediated release of GABA, but not of glutamate, simplifies the possibilities to explain the HFS mode of action, as the explanation now may concentrate on GABAergic axons only. Thus, we are analysing, on the basis of the pathophysiological grounds of the various syndromes treated with deep brain stimulation, whether a selective GABA release is a collective explanation of the mode of action of HFS. We suggest that selective GABA release indeed may needfully and sufficiently explain efficacy and side effects of HFS.

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GABAA autoreceptors enhance GABA release from human neocortex: towards a mechanism for high-frequency stimulation (HFS) in brain?

Cited by 23 publications

References 75 publications

The mode of action of electrical high frequency stimulation

The mode of action of electrical high frequency stimulation

Effects of antiepileptic drugs on GABA release from rat and human neocortical synaptosomes

Selective GABA release as a mechanistic basis of high-frequency stimulation used for the treatment of neuropsychiatric diseases

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