Activation of silent synapses with sustained but not decremental long-term potentiation

2007 ◽  
Vol 417 (1) ◽  
pp. 84-89 ◽  
Author(s):  
Michael R. Kasten ◽  
Yuan Fan ◽  
Paul E. Schulz
Keyword(s):  
Long Term Potentiation ◽  
Silent Synapses ◽  
Term Potentiation

AMPA Silencing Is a Prerequisite for Developmental Long-Term Potentiation in the Hippocampal CA1 Region

2008 ◽  
Vol 100 (5) ◽  
pp. 2605-2614 ◽  
Author(s):  
Therése Abrahamsson ◽  
Bengt Gustafsson ◽  
Eric Hanse
Keyword(s):  
Developmental Stages ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Silent Synapses ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Hippocampal Ca3

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) unsilencing is an often proposed expression mechanism both for developmental long-term potentiation (LTP), involved in circuitry refinement during brain development, and for mature LTP, involved in learning and memory. In the hippocampal CA3–CA1 connection naïve (nonstimulated) synapses are AMPA signaling and AMPA-silent synapses are created from naïve AMPA-signaling (AMPA-labile) synapses by test-pulse synaptic activation (AMPA silencing). To investigate to what extent LTPs at different developmental stages are explained by AMPA unsilencing, the amount of LTP obtained at these different developmental stages was related to the amount of AMPA silencing that preceded the induction of LTP. When examined in the second postnatal week Hebbian induction was found to produce no more stable potentiation than that causing a return to the naïve synaptic strength existing prior to the AMPA silencing. Moreover, in the absence of a preceding AMPA silencing Hebbian induction produced no stable potentiation above the naïve synaptic strength. Thus this early, or developmental, LTP is nothing more than an unsilencing (dedepression) and stabilization of the AMPA signaling that was lost by the prior AMPA silencing. This dedepression and stabilization of AMPA signaling was mimicked by the presence of the protein kinase A activator forskolin. As the relative degree of AMPA silencing decreased with development, LTP manifested itself more and more as a “genuine” potentiation (as opposed to a dedepression) not explained by unsilencing and stabilization of AMPA-labile synapses. This “genuine,” or mature, LTP rose from close to nothing of total LTP prior to postnatal day (P)13, to about 70% of total LTP at P16, and to about 90% of total LTP at P30. Developmental LTP, by stabilization of AMPA-labile synapses, thus seems adapted to select synaptic connections to the growing synaptic network. Mature LTP, by instead strengthening existing stable connections between cells, may then create functionally tightly connected cell assemblies within this network.

scholarly journals Silent synapses: what are they telling us about long-term potentiation?

2003 ◽  
Vol 358 (1432) ◽  
pp. 727-733 ◽  
Author(s):  
Dimitri M. Kullmann
Keyword(s):  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Glutamate Release ◽  
Postsynaptic Density ◽  
Long Term Potentiation ◽  
Silent Synapses ◽  
Term Potentiation ◽  
Silent Synapse ◽  
Cortical Synapses

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.

Quantifying the Magnitude of Changes in Synaptic Level Parameters With Long-Term Potentiation

2006 ◽  
Vol 96 (3) ◽  
pp. 1478-1491 ◽  
Author(s):  
William R. Holmes ◽  
Lawrence M. Grover
Keyword(s):  
Ampa Receptors ◽  
Single Channel ◽  
Long Term Potentiation ◽  
Channel Conductance ◽  
Single Channel Conductance ◽  
Vesicle Release ◽  
Silent Synapses ◽  
Term Potentiation ◽  
Synaptic Level

Experimental evidence supports a number of mechanisms for the synaptic change that occurs with long-term potentiation (LTP) including insertion of AMPA receptors, an increase in AMPA receptor single channel conductance, unmasking silent synapses, and increases in vesicle release probability. Here we combine experimental and modeling studies to quantify the magnitude of the change needed at the synaptic level to explain LTP with these proposed mechanisms. Whole cell patch recordings were used to measure excitatory postsynaptic potential (EPSP) amplitude in response to near minimal afferent stimulation before and after LTP induction in CA1 pyramidal cells. Detailed neuron and synapse level models were constructed to estimate quantitatively the changes needed to explain the experimental results. For cells in normal artificial cerebrospinal fluid (ACSF), we found a 60% average increase in EPSP amplitude with LTP. This was explained in the models by a 63% increase in the number of activated synapses, a 64% increase in the AMPA receptor single channel conductance, or a 73% increase in the number of AMPA receptors per potentiated synapse. When the percentage LTP was above the average, the required increases through the proposed mechanisms became nonlinear, particularly for increases in the number of receptors. Given constraints from other experimental studies, our quantification suggests that neither unmasking silent synapses nor increasing the numbers of AMPA receptors at synapses is sufficient to explain the magnitude of LTP we observed, but increasing AMPA single channel conductance or vesicle release probability can be sufficient. Our results are most compatible with a combination of mechanisms producing LTP.

scholarly journals Stress enhances fear by forming new synapses with greater capacity for long-term potentiation in the amygdala

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130151 ◽  
Author(s):  
Aparna Suvrathan ◽  
Sharath Bennur ◽  
Supriya Ghosh ◽  
Anupratap Tomar ◽  
Shobha Anilkumar ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Conditioned Fear ◽  
Brain Area ◽  
Long Term Potentiation ◽  
Silent Synapses ◽  
Term Potentiation ◽  
Emotional Behaviour ◽  
Synaptic Changes ◽  
And Function

Prolonged and severe stress leads to cognitive deficits, but facilitates emotional behaviour. Little is known about the synaptic basis for this contrast. Here, we report that in rats subjected to chronic immobilization stress, long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated synaptic responses are enhanced in principal neurons of the lateral amygdala, a brain area involved in fear memory formation. This is accompanied by electrophysiological and morphological changes consistent with the formation of ‘silent synapses’, containing only NMDARs. In parallel, chronic stress also reduces synaptic inhibition. Together, these synaptic changes would enable amygdalar neurons to undergo further experience-dependent modifications, leading to stronger fear memories. Consistent with this prediction, stressed animals exhibit enhanced conditioned fear. Hence, stress may leave its mark in the amygdala by generating new synapses with greater capacity for plasticity, thereby creating an ideal neuronal substrate for affective disorders. These findings also highlight the unique features of stress-induced plasticity in the amygdala that are strikingly different from the stress-induced impairment of structure and function in the hippocampus.

scholarly journals Fusion pore modulation as a presynaptic mechanism contributing to expression of long-term potentiation

2003 ◽  
Vol 358 (1432) ◽  
pp. 695-705 ◽  
Author(s):  
Sukwoo Choi ◽  
Jürgen Klingauf ◽  
Richard W. Tsien
Keyword(s):  
Nmda Receptor ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Quantitative Model ◽  
Fusion Pore ◽  
Silent Synapses ◽  
Term Potentiation ◽  
Presynaptic Mechanisms

Working on the idea that postsynaptic and presynaptic mechanisms of long-term potentiation (LTP) expression are not inherently mutually exclusive, we have looked for the existence and functionality of presynaptic mechanisms for augmenting transmitter release in hippocampal slices. Specifically, we asked if changes in glutamate release might contribute to the conversion of ‘silent synapses’ that show N -methyl-D-aspartate (NMDA) responses but no detectable α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) responses, to ones that exhibit both. Here, we review experiments where NMDA receptor responses provided a bioassay of cleft glutamate concentration, using opposition between peak [glu] cleft and a rapidly reversible antagonist, L-AP5. We discuss findings of a dramatic increase in peak [glu] cleft upon expression of pairing-induced LTP (Choi). We present simulations with a quantitative model of glutamatergic synaptic transmission that includes modulation of the presynaptic fusion pore, realistic cleft geometry and a distributed array of postsynaptic receptors and glutamate transporters. The modelling supports the idea that changes in the dynamics of glutamate release can contribute to synaptic unsilencing. We review direct evidence from Renger et al ., in accord with the modelling, that trading off the strength and duration of the glutamate transient can markedly alter AMPA receptor responses with little effect on NMDA receptor responses. An array of additional findings relevant to fusion pore modulation and its proposed contribution to LTP expression are considered.

Distinct Transmitter Release Properties Determine Differences in Short-Term Plasticity at Functional and Silent Synapses

2006 ◽  
Vol 95 (5) ◽  
pp. 3024-3034 ◽  
Author(s):  
Carolina Cabezas ◽  
Washington Buño
Keyword(s):  
Transmitter Release ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Lower Percentage ◽  
Functional Importance ◽  
Short Term ◽  
Short Term Plasticity ◽  
Silent Synapses ◽  
Term Potentiation

Recent evidence suggests that functional and silent synapses are not only postsynaptically different but also presynaptically distinct. The presynaptic differences may be of functional importance in memory formation because a proposed mechanism for long-term potentiation is the conversion of silent synapses into functional ones. However, there is little direct experimentally evidence of these differences. We have investigated the transmitter release properties of functional and silent Schaffer collateral synapses and show that on the average functional synapses displayed a lower percentage of failures and higher excitatory postsynaptic current (EPSC) amplitudes than silent synapses at +60 mV. Moreover, functional but not silent synapses show paired-pulse facilitation (PPF) at +60 mV and thus presynaptic short-term plasticity will be distinct in the two types of synapse. We examined whether intraterminal endoplasmic reticulum Ca2+ stores influenced the release properties of these synapses. Ryanodine (100 μM) and thapsigargin (1 μM) increased the percentage of failures and decreased both the EPSC amplitude and PPF in functional synapses. Caffeine (10 mM) had the opposite effects. In contrast, silent synapses were insensitive to both ryanodine and caffeine. Hence we have identified differences in the release properties of functional and silent synapses, suggesting that synaptic terminals of functional synapses express regulatory molecular mechanisms that are absent in silent synapses.

scholarly journals Incorporation of inwardly rectifying AMPA receptors at silent synapses during hippocampal long-term potentiation

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130156 ◽  
Author(s):  
Daiju Morita ◽  
Jong Cheol Rah ◽  
John T. R. Isaac
Keyword(s):  
Ampa Receptors ◽  
Calcium Influx ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Subunit Composition ◽  
Common Mechanism ◽  
Silent Synapses ◽  
Term Potentiation ◽  
Inwardly Rectifying

Despite decades of study, the mechanisms by which synapses express the increase in strength during long-term potentiation (LTP) remain an area of intense interest. Here, we have studied how AMPA receptor subunit composition changes during the early phases of hippocampal LTP in CA1 pyramidal neurons. We studied LTP at silent synapses that initially lack AMPA receptors, but contain NMDA receptors. We show that strongly inwardly rectifying AMPA receptors are initially incorporated at silent synapses during LTP and are then subsequently replaced by non-rectifying AMPA receptors. These findings suggest that silent synapses initially incorporate GluA2-lacking, calcium-permeable AMPA receptors during LTP that are then replaced by GluA2-containing calcium-impermeable receptors. We also show that LTP consolidation at CA1 synapses requires a rise in intracellular calcium concentration during the early phase of expression, indicating that calcium influx through the GluA2-lacking AMPA receptors drives their replacement by GluA2-containing receptors during LTP consolidation. Taken together with previous studies in hippocampus and in other brain regions, these findings suggest that a common mechanism for the expression of activity-dependent glutamatergic synaptic plasticity involves the regulation of GluA2-subunit composition and highlights a critical role for silent synapses in this process.

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