L-Type Voltage-Gated Ca<sup>2+</sup>Channels: A Single Molecular Switch for Long-Term Potentiation/Long-Term Depression-Like Plasticity and Activity-Dependent Metaplasticity in Humans

Wankerl, Katharina; Weise, David; Gentner, R.; Rumpf, Jost‐Julian; Claßen, Joseph

doi:10.1523/jneurosci.4673-09.2010

Cited by 101 publications

(83 citation statements)

References 51 publications

(77 reference statements)

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“…EtOH at low concentrations of p25 mM resulted in NMDAR inhibition in various experimental preparations (Lovinger et al, 1989(Lovinger et al, , 1990Weitlauf and Woodward, 2008), and in significant suppression of LTP (Blitzer et al, 1990;Morrisett and Swartzwelder, 1993), although other studies failed to reported significant LTP suppression by low concentrations of EtOH (Pyapali et al, 1999;Schummers et al, 1997). Taken together, NMDAR inhibition may have contributed to the suppressive effect of low-dose EtOH on LTP-like plasticity in our study, in agreement with previous studies that have demonstrated suppression of LTP-like plasticity by specific pharmacological NMDAR blockade (Stefan et al, 2002;Wankerl et al, 2010).…”

Section: Drug Effects On Pas Ltp -Induced Ltp-like Increase Of Mep Iosupporting

confidence: 92%

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Lücke

Heidegger

Röhner

et al. 2014

Neuropsychopharmacol

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Ingesting ethanol (EtOH) at low doses during social drinking is a common human behavior for its facilitating effects on social interactions. However, low-dose EtOH may have also detrimental effects that so far are underexplored. Here we sought to test the effects of lowdose EtOH on long-term potentiation (LTP)-like plasticity in human motor cortex. Previous cellular experiments showed that low-dose EtOH potentiates extrasynaptic GABAAR and reduces NMDAR-mediated currents, processes that would limit the expression of LTP. Paired associative transcranial magnetic stimulation (PAS LTP ) was employed in nine healthy subjects for induction of LTP-like plasticity, indexed by a long-term increase in motor-evoked potential input-output curves. Synaptic a1-GABAAR function was measured by saccadic peak velocity (SPV). Very low doses of EtOH (resulting in blood concentrations of o5 mM) suppressed LTP-like plasticity but did not affect SPV when compared with a placebo condition. In contrast, 1 mg of alprazolam, a classical benzodiazepine, or 10 mg of zolpidem, a non-benzodiazepine hypnotic, decreased SPV but did not significantly affect LTP-like plasticity when compared with placebo. This double dissociation of low-dose EtOH vs alprazolam/zolpidem effects is best explained by the putatively high affinity of EtOH but not alprazolam/zolpidem to extrasynaptic GABAARs and to NMDARs. Findings suggest that enhancement of extrasynaptic GABAARmediated tonic inhibition and/or reduction of NMDAR-mediated neurotransmission by EtOH blocks LTP-like plasticity in human cortex at very low doses that are easily reached during social drinking. Therefore, low-dose EtOH may jeopardize LTP-dependent processes, such as learning and memory formation.

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Section: Drug Effects On Pas Ltp -Induced Ltp-like Increase Of Mep Iosupporting

confidence: 92%

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Lücke

Heidegger

Röhner

et al. 2014

Neuropsychopharmacol

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“…The level of postsynaptic calcium influx determines the induction of synaptic LTP or its opposite, long-term depression (LTD). Fast increases in intracellular calcium inflows lead to LTP of the synapse (Wankerl et al, 2010). In this study, MEP amplitudes were increased after PAS only in healthy controls, suggesting that the mechanisms underlying LTP induction were impaired in the motor cortex of those with depression.…”

Section: Discussionmentioning

confidence: 48%

Neuroplasticity in Depressed Individuals Compared with Healthy Controls

Player

Taylor

Weickert

et al. 2013

Neuropsychopharmacol

102

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Several lines of evidence suggest that neuroplasticity is impaired in depression. This study aimed to compare neuroplasticity in 23 subjects with DSM-IV major depressive episode and 23 age-and gender-matched healthy controls, using an objective test that is independent of subject effort and motivation. Neuroplasticity was assessed in the motor cortex using a brain stimulation paradigm known as paired associative stimulation (PAS), which induces transient changes in motor cortical function. Motor cortical excitability was assessed before and after PAS using single-pulse transcranial magnetic stimulation (TMS) to induce motor evoked potentials (MEPs) in a hand muscle. After PAS, MEP amplitudes significantly increased in healthy controls compared with depressed subjects (P ¼ 0.002). The functional significance of motor cortical changes was assessed using a motor learning task-a computerized version of the rotor pursuit task. Healthy controls also performed better on motor learning (P ¼ 0.02). BDNF blood levels and genotype were assayed to determine any relationship with motor cortical plasticity. However, PAS results did not correlate with motor learning, nor appear to be related to BDNF measures. The significance of these findings is that it provides one of the first direct demonstrations of reduced neuroplasticity in depressed subjects, using an objective test.

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“…(2014) [112] Hand immobilization/PAS Eight hours of hand immobilization significantly reduce the inhibitory effects of PAS-10ms while enhancing the facilitatory effects of PAS-25ms.…”

Section: Text Box 1 Definition Boxmentioning

confidence: 99%

Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation

et al. 2015

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Homeostatic plasticity is thought to stabilize neural activity around a set point within a physiologically reasonable dynamic range. Over the last ten years, a wide range of non-invasive transcranial brain stimulation (NTBS) techniques have been used to probe homeostatic control of cortical plasticity in the intact human brain. Here, we review different NTBS approaches to study homeostatic plasticity on a systems level and relate the findings to both, physiological evidence from in vitro studies and to a theoretical framework of homeostatic function. We highlight differences between homeostatic and other non-homeostatic forms of plasticity and we examine the contribution of sleep in restoring synaptic homeostasis. Finally, we discuss the growing number of studies showing that abnormal homeostatic plasticity may be associated to a range of neuropsychiatric diseases.

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L-Type Voltage-Gated Ca²⁺Channels: A Single Molecular Switch for Long-Term Potentiation/Long-Term Depression-Like Plasticity and Activity-Dependent Metaplasticity in Humans

Cited by 101 publications

References 51 publications

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Neuroplasticity in Depressed Individuals Compared with Healthy Controls

Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation

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L-Type Voltage-Gated Ca2+Channels: A Single Molecular Switch for Long-Term Potentiation/Long-Term Depression-Like Plasticity and Activity-Dependent Metaplasticity in Humans

Cited by 101 publications

References 51 publications

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Neuroplasticity in Depressed Individuals Compared with Healthy Controls

Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation

Contact Info

Product

Resources

About

L-Type Voltage-Gated Ca²⁺Channels: A Single Molecular Switch for Long-Term Potentiation/Long-Term Depression-Like Plasticity and Activity-Dependent Metaplasticity in Humans