Involvement of silent synapses in the induction of long-term potentiation and long-term depression in neocortical and hippocampal neurons

At several cortical synapses glutamate release events can be mediated exclusively by NMDA receptors, with no detectable contribution from AMPA receptors. This observation was originally made by comparing the trial-to-trial variability of the two components of synaptic signals evoked in hippocampal neurons, and was subsequently confirmed by recording apparently pure NMDA receptor-mediated EPSCs with stimulation of small numbers of axons. It has come to be known as the ‘silent synapse’ phenomenon, and is widely assumed to be caused by the absence of functional AMPA receptors, which can, however, be recruited into the postsynaptic density by long-term potentiation (LTP) induction. Thus, it provides an important impetus for relating AMPA receptor trafficking mechanisms to the expression of LTP, a theme that is taken up elsewhere in this issue. This article draws attention to several findings that call for caution in identifying silent synapses exclusively with synapses without AMPA receptors. In addition, it attempts to identify several missing pieces of evidence that are required to show that unsilencing of such synapses is entirely accounted for by insertion of AMPA receptors into the postsynaptic density. Some aspects of the early stages of LTP expression remain open to alternative explanations.

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Simultaneous NMDA-Dependent Long-Term Potentiation of EPSCs and Long-Term Depression of IPSCs in Cultured Rat Hippocampal Neurons

Journal of Neuroscience ◽

10.1523/jneurosci.2964-05.2006 ◽

2006 ◽

Vol 26 (4) ◽

pp. 1199-1210 ◽

Cited By ~ 20

Author(s):

M. Ivenshitz

Keyword(s):

Hippocampal Neurons ◽

Long Term Potentiation ◽

Long Term Depression ◽

Term Potentiation

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Calcium signals in long-term potentiation and long-term depression

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y99-079 ◽

1999 ◽

Vol 77 (9) ◽

pp. 722-734 ◽

Cited By ~ 15

Author(s):

John A Connor ◽

Jeffrey Petrozzino ◽

Lucas D Pozzo-Miller ◽

Satoru Otani

Keyword(s):

Nmda Receptor ◽

Neuronal Plasticity ◽

Hippocampal Neurons ◽

Low Frequency ◽

Long Term Potentiation ◽

Long Term Depression ◽

Metabotropic Receptor ◽

Ca1 Neurons ◽

Term Potentiation

We describe postsynaptic Ca2+ signals that subserve induction of two forms of neuronal plasticity, long-term potentiation (LTP) and long-term depression (LTD), in rat hippocampal neurons. The common induction protocol for LTP, a 1-s, 50-Hz tetanus, generates Ca2+ increases of about 50 µM in dendritic spines of CA1 neurons. These very large increases, measured using a low affinity indicator (Mg fura 5), were found only in the spines and tertiary dendrites, and were dependent upon influx through N-methyl-D-aspartate (NMDA) gated channels. High affinity Ca2+ indicators (e.g., fura 2) are unable to demonstrate these events. In acute slices, neighboring dendritic branches often showed very different responses to a tetanus, and in some instances, neighboring spines on the same dendrite responded differently. LTD in mature CA1 neurons was induced by a low frequency stimulus protocol (2 Hz, 900 pulses), in the presence of GABA- and NMDA-receptor blockers. This LTD protocol produced dendritic Ca2+ increases of <1 µM. Duration of the Ca2+ increase was ~30 s and was due to voltage-gated Ca2+ influx. Finally, the ability of synaptically addressed Ca2+ stores to release Ca2+ was studied in CA3 neurons and was found to require immediate preloading and high intensity presynaptic stimulation, conditions unlike normal LTP-LTD protocols.Key words: long-term potentiation, long-term depression, Ca2+, neuronal plasticity, fluorescence imaging, N-methyl-D-aspartate (NMDA) receptor, metabotropic receptor.

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