Bidirectional synaptic plasticity induced by conditioned stimulations with different number of pulse at hippocampal CA1 synapses: Roles ofN‐methyl‐D‐aspartate and metabotropic glutamate receptors

Abstract

In the mammalian brain, the hippocampus has been established as a principle structure for learning and memory processes, which involve synaptic plasticity. Although a relationship between synaptic plasticity and stimulation frequency has been reported in numerous studies, little is known about the importance of pulse number on synaptic plasticity. Here we investigated whether the pulse number can modulate bidirectional plasticity in hippocampal CA1 areas. When a CA1 area was induced by a paired-pulse (PP) with a 10-ms interval, the strength of the synapse was altered to form a long-term depression (LTD), with a 68 ± 4% decrease in expression. The PP-induced LTD (PP-LTD) was blocked by the metabotropic glutamate receptors subtype 5 (mGluR5) antagonist MPEP, suggesting that the PP-LTD relied on the activation of GluR5. In addition, this modulation of LTD was protein kinase C (PKC)- and Group II mGluR-independent. However, when increasing the pulse number to 4 and 6, potentiated synaptic strength was observed, which was N-methyl-D-aspartate receptor (NMDAR)-dependent but mGluR5-independent. Surprisingly, when blocking mGluR, the synaptic efficacy induced by triple-pulse stimulation was altered to form a long-term potentiation (LTP) with a 142 ± 7% enhancement, and was further blocked by NMDA antagonist APV. Following treatment with APV and PKC blocker chelerythrine, the LTP expression induced by 4- and 6-pulse stimulation was switched to LTD. We suggest that CA1 synaptic plasticity is regulated by the result of competition between NMDA and mGluR5 receptors. We suggest that the pulse number can bidirectionally modulate synaptic plasticity through the activation of NMDA and mGluR5 in hippocampal CA1 areas.

Hippocampal Protein Kinase C Signaling Mediates the Short-Term Memory Impairment Induced by Delta9-Tetrahydrocannabinol

“…The use of PKC and mTORC1 inhibitors, at concentrations that do not affect memory on their own, demonstrated the independent mechanisms underlying the short-term (PKC signaling) and long-term (mTORC1 signaling) object-recognition memory deficits produced by THC. In this regard, PKC signaling has been shown to regulate synaptic plasticity at CA1 synapses (Hsu et al, 2011). At this level, PKC signaling is implicated in facilitating longterm plasticity by reducing the threshold necessary for longterm potentiation induction (Miura et al, 2002).…”

Separate Ionotropic and Metabotropic Glutamate Receptor Functions in Depotentiation vs. LTP: A Distinct Role for Group1 mGluR Subtypes and NMDARs

“…Hsu et al (2011) suggested recently that “CA1 synaptic plasticity is regulated by the result of competition between NMDARs and mGluR5 receptors”. Although a similar competition is likely to occur also between NMDARs and mGluR1, an interaction between mGluR1 and metabotropic NMDAR actions cannot be simply explained by data from published studies because they are exclusively based upon the use of the competitive NMDAR antagonist D-AP5 which does not allow to distinguish between ionotropic and metabotropic NMDAR actions.…”

The repetition timing of high frequency afferent stimulation drives the bidirectional plasticity at central synapses in the rat medial vestibular nuclei

“…It is well known that induction of LTP and LTD depends on different levels of postsynaptic Ca 2+ increasing through NMDAR, metabotropic glutamate receptor or voltagegated Ca 2+ channel activation (Neveu and Zucker, 1996;Artola and Singer, 1993;Hansel et al, 1997;Malenka and Nicoll, 1999;Yang et al, 1999;Zucher, 1999;Cormier et al, 2001;Cho et al, 2001;Lisman, 2001;Gall et al, 2005;Anwyl, 2006;D'Errico et al, 2009;Fujii et al, 2010;Vogt and Canepari, 2010;Hsu et al, 2011) and decreasing by buffering mechanisms (Malenka et al, 1992;Gold and Bear, 1994). On this ground, we can suggest that in the vestibular neurons a change in the IBI modifies the ratio between Ca 2+ enhancement during the stimulus, due to the NMDAR and/or voltage-dependent Ca 2+ channel influx (Serafin et al, 1991;Takahashi et al, 1994b), and its decay during the pause, leading to different postsynaptic Ca 2+ levels.…”