Thapsigargin blocks STP and LTP related calcium enhancements in hippocampal CA1 area

Matias, Carlos M.; Dionisio, José; Quinta‐Ferreira, Mário

doi:10.1097/00001756-200212200-00039

Cited by 15 publications

(9 citation statements)

References 25 publications

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“…Interestingly, neither SERCA inhibitor affected WT LTP induced by the 200-Hz induction protocol. This is consistent with previous results that showed that SERCA inhibitors affect LTP induced only by weak (but not strong, e.g., 200 Hz) stimulation protocols (Behnisch and Reymann, 1995;Matias et al, 2002;Zhang et al, 2009). Thus, in the presence of CPA, WT fEPSP 5 (p=0.210) and fEPSP 360 (p=0.680) were not significantly different from those seen in the absence of CPA (16-52 slices, 6-15 mice).…”

Section: Resultssupporting

confidence: 93%

Dysregulation of Presynaptic Calcium and Synaptic Plasticity in a Mouse Model of 22q11 Deletion Syndrome

Earls¹,

Bayazitov²,

Fricke³

et al. 2010

J. Neurosci.

104

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The 22q11 deletion syndrome (22q11DS) is characterized by cognitive decline and increased risk of psychiatric disorders, mainly schizophrenia. The molecular mechanisms of neuronal dysfunction in cognitive symptoms of 22q11DS are poorly understood. Here, we report that a mouse model of 22q11DS, the Df(16)1/؉ mouse, exhibits substantially enhanced short-and long-term synaptic plasticity at hippocampal CA3-CA1 synapses, which coincides with deficits in hippocampus-dependent spatial memory. These changes are evident in mature but not young animals. Electrophysiological, two-photon imaging and glutamate uncaging, and electron microscopic assays in acute brain slices showed that enhanced neurotransmitter release but not altered postsynaptic function or structure caused these changes. Enhanced neurotransmitter release in Df(16)1/؉ mice coincided with altered calcium kinetics in CA3 presynaptic terminals and upregulated sarco(endo)plasmic reticulum calcium-ATPase type 2 (SERCA2). SERCA inhibitors rescued synaptic phenotypes of Df(16)1/؉ mice. Thus, presynaptic SERCA2 upregulation may be a pathogenic event contributing to the cognitive symptoms of 22q11DS.

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Section: Resultssupporting

confidence: 93%

Dysregulation of Presynaptic Calcium and Synaptic Plasticity in a Mouse Model of 22q11 Deletion Syndrome

Earls¹,

Bayazitov²,

Fricke³

et al. 2010

J. Neurosci.

104

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“…While the results of studies using MCPG do not exclude a role for IP 3 receptors in altered synaptic plasticity with age, the inability of MCPG to facilitate LTP indicates that the mGluR-IP 3 pathway does not participate in inhibiting LTP under our experimental conditions. Other researchers have noted developmental changes in the mGluR-IP 3 pathway such that activation of this pathway can reduced cell excitability, decrease LTP and promote depression of synaptic transmission in neonates (Nishiyama et al 2000), while in juvenile or young adult animals, the LTP threshold is reduced by activation of mGluRs (Brown et al 2000;Cohen et al 1999;Matias et al 2002;Thomas et al 1996). Under conditions in which mGluR activation facilitates LTP induction, an increased cell excitability involving a reduction in the AHP and increased current through NMDA receptors is observed as well (Cohen et al 1999;Madison and Nicoll 1986;Pisani et al 1997;Thomas et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Long-Term Potentiation During Aging Is Masked by Processes Involving Intracellular Calcium Stores

Kumar

Foster

2004

Journal of Neurophysiology

119

108

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The contribution of Ca(2+) release from intracellular Ca(2+) stores (ICS) for regulation of synaptic plasticity thresholds during aging was investigated in hippocampal slices of old (22-24 mo) and young adult (5-8 mo) male Fischer 344 rats. Inhibition of Ca(2+)-induced Ca(2+) release by thapsigargin, cyclopiazonic acid (CPA), or ryanodine during pattern stimulation near the threshold for synaptic modification (5 Hz, 900 pulses) selectively induced long-term potentiation (LTP) to CA1 Schaffer collateral synapses of old rats. Increased synaptic strength was specific to test pathways and blocked by AP-5. Intracellular recordings demonstrated that ICS plays a role in the augmentation of the afterhyperpolarization (AHP) in old rats. The decrease in the AHP by ICS inhibition was reversed by the L-channel agonist, Bay K8644. Under conditions of ICS inhibition and a Bay K8644-mediated enhancement of the AHP, pattern stimulation failed to induce LTP, consistent with the idea that the AHP amplitude shapes the threshold for LTP induction. Finally, ICS inhibition was associated with an increase in the N-methyl-d-aspartate (NMDA) receptor component of synaptic transmission in old animals. This increase in the synaptic response was blocked by the calcineurin inhibitor FK506. The results reveal an age-related increase in susceptibility to LTP-induction that is normally inhibited by ICS and suggest that the age-related shift in Ca(2+) regulation and Ca(2+)-dependent synaptic plasticity is coupled to changes in cell excitability and NMDA receptor function through ICS.

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“…Although pharmacological perturbation of SERCA in for the conclusions based on pharmacological evidence that SERCA-mediated calcium sequestration is operative other model systems using relatively specific drugs such as thapsigargin and cyclopiazonic acid has been used in the presynaptic terminal (Matias et al 2002;Lauri et al 2003). extensively, the elegant simplicity, precision, and clarity of a genetic analysis remains unparalleled.…”

Section: Gal4) and Three Muscle Drivers (Mhc-gal4 24b-gal4mentioning

confidence: 99%

Analysis of Conditional Paralytic Mutants in Drosophila Sarco-Endoplasmic Reticulum Calcium ATPase Reveals Novel Mechanisms for Regulating Membrane Excitability

et al. 2005

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Individual contributions made by different calcium release and sequestration mechanisms to various aspects of excitable cell physiology are incompletely understood. SERCA, a sarco-endoplasmic reticulum calcium ATPase, being the main agent for calcium uptake into the ER, plays a central role in this process. By isolation and extensive characterization of conditional mutations in the Drosophila SERCA gene, we describe novel roles of this key protein in neuromuscular physiology and enable a genetic analysis of SERCA function. At motor nerve terminals, SERCA inhibition retards calcium sequestration and reduces the amplitude of evoked excitatory junctional currents. This suggests a direct contribution of store-derived calcium in determining the quantal content of evoked release. Conditional paralysis of SERCA mutants is also marked by prolonged neural activity-driven muscle contraction, thus reflecting the phylogenetically conserved role of SERCA in terminating contraction. Further analysis of ionic currents from mutants uncovers SERCA-dependent mechanisms regulating voltage-gated calcium channels and calcium-activated potassium channels that together control muscle excitability. Finally, our identification of dominant lossof-function mutations in SERCA indicates novel intra-and intermolecular interactions for SERCA in vivo, overlooked by current structural models.

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Thapsigargin blocks STP and LTP related calcium enhancements in hippocampal CA1 area

Cited by 15 publications

References 25 publications

Dysregulation of Presynaptic Calcium and Synaptic Plasticity in a Mouse Model of 22q11 Deletion Syndrome

Dysregulation of Presynaptic Calcium and Synaptic Plasticity in a Mouse Model of 22q11 Deletion Syndrome

Enhanced Long-Term Potentiation During Aging Is Masked by Processes Involving Intracellular Calcium Stores

Analysis of Conditional Paralytic Mutants in Drosophila Sarco-Endoplasmic Reticulum Calcium ATPase Reveals Novel Mechanisms for Regulating Membrane Excitability

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