Evidence for NMDA and mGlu Receptor-Dependent Long-Term Potentiation of Mossy Fiber–Granule Cell Transmission in Rat Cerebellum

1999 ◽  
Vol 81 (1) ◽  
pp. 277-287 ◽  
Author(s):  
Egidio D'Angelo ◽  
Paola Rossi ◽  
Simona Armano ◽  
Vanni Taglietti
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Granule Cell ◽  
High Frequency ◽  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Mglu Receptor ◽  
Rat Cerebellum ◽  
Term Potentiation

D'Angelo, Egidio, Paola Rossi, Simona Armano, and Vanni Taglietti. Evidence for NMDA and mGlu receptor-dependent long-term potentiation of mossy fiber–granule cell transmission in rat cerebellum. J. Neurophysiol. 81: 277–287, 1999. Long-term potentiation (LTP) is a form of synaptic plasticity that can be revealed at numerous hippocampal and neocortical synapses following high-frequency activation of N-methyl-d-aspartate (NMDA) receptors. However, it was not known whether LTP could be induced at the mossy fiber–granule cell relay of cerebellum. This is a particularly interesting issue because theories of the cerebellum do not consider or even explicitly negate the existence of mossy fiber–granule cell synaptic plasticity. Here we show that high-frequency mossy fiber stimulation paired with granule cell membrane depolarization (−40 mV) leads to LTP of granule cell excitatory postsynaptic currents (EPSCs). Pairing with a relatively hyperpolarized potential (−60 mV) or in the presence of NMDA receptor blockers [5-amino-d-phosphonovaleric acid (APV) and 7-chloro-kynurenic acid (7-Cl-Kyn)] prevented LTP, suggesting that the induction process involves a voltage-dependent NMDA receptor activation. Metabotropic glutamate receptors were also involved because blocking them with (+)-α-methyl-4-carboxyphenyl-glycine (MCPG) prevented potentiation. At the cytoplasmic level, EPSC potentiation required a Ca2+ increase and protein kinase C (PKC) activation. Potentiation was expressed through an increase in both the NMDA and non-NMDA receptor-mediated current and by an NMDA current slowdown, suggesting that complex mechanisms control synaptic efficacy during LTP. LTP at the mossy fiber–granule cell synapse provides the cerebellar network with a large reservoir for memory storage, which may be needed to optimize pattern recognition and, ultimately, cerebellar learning and computation.

scholarly journals (2S,6S)- and (2R,6R)-hydroxynorketamine inhibit the induction of NMDA receptor-dependent LTP at hippocampal CA1 synapses in mice

2020 ◽  
Vol 4 ◽  
pp. 239821282095784
Author(s):  
Heather Kang ◽  
Pojeong Park ◽  
Muchun Han ◽  
Patrick Tidball ◽  
John Georgiou ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Long Term Potentiation ◽  
Aspartate Receptor ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Mouse Hippocampus ◽  
Site Of Action ◽  
A Site

The ketamine metabolite (2 R,6 R)-hydroxynorketamine has been proposed to have rapid and persistent antidepressant actions in rodents, but its mechanism of action is controversial. We have compared the ability of ( R,S)-ketamine with the (2 S,6 S)- and (2 R,6 R)-isomers of hydroxynorketamine to affect the induction of N-methyl-d-aspartate receptor–dependent long-term potentiation in the mouse hippocampus. Following pre-incubation of these compounds, we observed a concentration-dependent (1–10 μM) inhibition of long-term potentiation by ketamine and a similar effect of (2 S,6 S)-hydroxynorketamine. At a concentration of 10 μM, (2 R,6 R)-hydroxynorketamine also inhibited the induction of long-term potentiation. These findings raise the possibility that inhibition of N-methyl-d-aspartate receptor–mediated synaptic plasticity is a site of action of the hydroxynorketamine metabolites with respect to their rapid and long-lasting antidepressant-like effects.

Regional and Postnatal Heterogeneity of Activity-Dependent Long-Term Changes in Synaptic Efficacy in the Dorsal Striatum

2000 ◽  
Vol 84 (3) ◽  
pp. 1422-1429 ◽  
Author(s):  
John G. Partridge ◽  
Ka-Choi Tang ◽  
David M. Lovinger
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Brain Region ◽  
High Frequency ◽  
Long Term Potentiation ◽  
Rat Striatum ◽  
Synaptic Efficacy ◽  
Dependent Form ◽  
Activity Dependent

High-frequency activation of excitatory striatal synapses produces lasting changes in synaptic efficacy that may contribute to motor and cognitive functions. While some of the mechanisms responsible for the induction of long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic responses at striatal synapses have been characterized, much less is known about the factors that govern the direction of synaptic plasticity in this brain region. Here we report heterogeneous activity-dependent changes in the direction of synaptic strength in subregions of the developing rat striatum. Neurons in the dorsolateral region of the anterior striatum tended to express LTD after high-frequency afferent stimulation (HFS) in slices from animals aged P15–P34. However, HFS in dorsolateral striatum from P12-P14 elicited an N-methyl-d-aspartate (NMDA) receptor-dependent form of LTP. Synapses in the dorsomedial anterior striatum exhibited a propensity to express an NMDA-receptor dependent form of LTP across the entire developmental time period examined. The NMDA receptor antagonist (±)-2-amino-5-phosphopentanoic acid (APV) inhibited evoked excitatory postsynaptic potentials recorded in striatum obtained from P12–P15 rats but had little effect in striatum from older animals. The expression of multiple forms of synaptic plasticity in the striatum suggests mechanisms by which this brain region plays pivotal roles in the acquisition or encoding of some forms of motor sequencing and stereotypical behaviors.

scholarly journals Xenon Attenuates Hippocampal Long-term Potentiation by Diminishing Synaptic and Extrasynaptic N -methyl-D-aspartate Receptor Currents

2012 ◽  
Vol 116 (3) ◽  
pp. 673-682 ◽  
Author(s):  
Stephan Kratzer ◽  
Corinna Mattusch ◽  
Eberhard Kochs ◽  
Matthias Eder ◽  
Rainer Haseneder ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
High Frequency ◽  
Brain Slices ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Field Potentials ◽  
Aspartate Receptor ◽  
Term Potentiation ◽  
Frequency Stimulation

Background The memory-blocking properties of general anesthetics are of high clinical relevance and scientific interest. The inhalational anesthetic xenon antagonizes N-methyl-D-aspartate (NMDA) receptors. It is unknown if xenon affects long-term potentiation (LTP), a cellular correlate for memory formation. In hippocampal brain slices, the authors investigated in area CA1 whether xenon affects LTP, NMDA receptor-mediated neurotransmission, and intracellular calcium concentrations. Methods In sagittal murine hippocampal brain slices, the authors investigated the effects of xenon on LTP by recording excitatory postsynaptic field potentials. Using fluorometric calcium imaging, the authors tested the influence of xenon on calcium influx during high-frequency stimulation. In addition, using the patch-clamp technique, the xenon effect on synaptic and extrasynaptic NMDA receptors and L-type calcium channels was examined. Results In the absence of xenon, high-frequency stimulation reliably induced LTP and potentiated field potential slopes to (mean ± SEM) 127.2 ± 5.8% (P < 0.001). In the presence of xenon, high-frequency stimulation induced only a short-term potentiation, and field potentials returned to baseline level after 15-20 min (105.9 ± 2.9%; P = 0.090). NMDA receptor-mediated excitatory postsynaptic currents were reduced reversibly by xenon to 65.9 ± 9.4% (P = 0.007) of control. When extrasynaptic receptors were activated, xenon decreased NMDA currents to 58.2 ± 5.8% (P < 0.001). Xenon reduced the increase in intracellular calcium during high-frequency stimulation without affecting L-type calcium channels. Conclusions N-methyl-D-aspartate receptor activation is crucial for the induction of CA1 LTP. Thus, the depression of NMDA receptor-mediated neurotransmission presumably contributes to the blockade of LTP under xenon. Because LTP is assumed to be involved in learning and memory, its blockade might be a key mechanism for xenon's amnestic properties.

scholarly journals Increased neurotransmitter release during long-term potentiation at mossy fibre-granule cell synapses in rat cerebellum

2004 ◽  
Vol 557 (3) ◽  
pp. 843-861 ◽  
Author(s):  
Elisabetta Sola ◽  
Francesca Prestori ◽  
Paola Rossi ◽  
Vanni Taglietti ◽  
Egidio D'Angelo
Keyword(s):  
Granule Cell ◽  
Neurotransmitter Release ◽  
Long Term Potentiation ◽  
Mossy Fibre ◽  
Rat Cerebellum ◽  
Term Potentiation

scholarly journals NMDA Receptor Antagonists Reveal Age-Dependent Differences in the Properties of Visual Cortical Plasticity

2008 ◽  
Vol 100 (4) ◽  
pp. 1936-1948 ◽  
Author(s):  
Jacqueline de Marchena ◽  
Adam C. Roberts ◽  
Paul G. Middlebrooks ◽  
Vera Valakh ◽  
Koji Yashiro ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Cortical Plasticity ◽  
Long Term Potentiation ◽  
Underlying Mechanism ◽  
Developmental Shift ◽  
Term Potentiation ◽  
Nmdar Activation ◽  
Visual Cortical

The suggestion that NMDA receptor (NMDAR)-dependent plasticity is subunit specific, with NR2B-types required for long-term depression (LTD) and NR2A-types critical for the induction of long-term potentiation (LTP), has generated much attention and considerable debate. By investigating the suggested subunit-specific roles of NMDARs in the mouse primary visual cortex over development, we report several important findings that clarify the roles of NMDAR subtypes in synaptic plasticity. We observed that LTD was not attenuated by application of ifenprodil, an NR2B-type antagonist, or NVP-AAM007, a less selective NR2A-type antagonist. However, we were surprised that NVP-AAM007 completely blocked adult LTP (postnatal day (P) 45–90), while only modestly affecting juvenile LTP (P21-28). To assess whether this developmental transition reflected an increasing role for NR2A-type receptors with maturity, we characterized the specificity of NVP-AAM007. We found not only that NVP-AAM007 lacks discernable subunit specificity but also that the effects of NVP-AAM077 on LTP could be mimicked using subsaturating concentrations of APV, a global NMDAR antagonist. These results indicate that the effects of NVP-AAM077 on synaptic plasticity are largely explained by nonspecific blockade of NMDARs. Moreover our findings are the first to reveal a developmental increase in the sensitivity of LTP to NMDAR antagonism. We suggest that discrepant reports describing the effect of NVP-AAM077 on LTP may be partially explained by this developmental shift in the properties of LTP. These results indicate that the degree of NMDAR activation required for LTP increases with development, providing insight into a novel underlying mechanism governing the properties of synaptic plasticity.

scholarly journals Dentate gyrus granule cell firing patterns can induce mossy fiber long-term potentiation in vitro

Hippocampus ◽  
2010 ◽  
Vol 21 (11) ◽  
pp. 1157-1168 ◽  
Author(s):  
Rajen Mistry ◽  
Siobhan Dennis ◽  
Matthew Frerking ◽  
Jack R. Mellor
Keyword(s):  
Dentate Gyrus ◽  
Granule Cell ◽  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Firing Patterns ◽  
Term Potentiation ◽  
Cell Firing

scholarly journals NMDA receptor-dependent long-term potentiation comprises a family of temporally overlapping forms of synaptic plasticity that are induced by different patterns of stimulation

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130131 ◽  
Author(s):  
Pojeong Park ◽  
Arturas Volianskis ◽  
Thomas M. Sanderson ◽  
Zuner A. Bortolotto ◽  
David E. Jane ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Recent Work ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Extensive Literature ◽  
Synaptic Activation ◽  
Aspartate Receptor ◽  
Term Potentiation

N -methyl- d -aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) is extensively studied since it is believed to use the same molecular mechanisms that are required for many forms of learning and memory. Unfortunately, many controversies exist, not least the seemingly simple issue concerning the locus of expression of LTP. Here, we review our recent work and some of the extensive literature on this topic and present new data that collectively suggest that LTP can be explained, during its first few hours, by the coexistence of at least three mechanistically distinct processes that are all triggered by the synaptic activation of NMDARs.

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