Calcineurin Participation in Hebbian and Homeostatic Plasticity Associated With Extinction

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.685838 ◽

2021 ◽

Vol 15 ◽

Author(s):

Salma E. Reyes-García ◽

Martha L. Escobar

Keyword(s):

Molecular Mechanisms ◽

Long Term Potentiation ◽

Underlying Mechanism ◽

Homeostatic Plasticity ◽

Extinction Process ◽

Hebbian Plasticity ◽

Term Potentiation ◽

Dependent Modification ◽

Activity Dependent

In nature, animals need to adapt to constant changes in their environment. Learning and memory are cognitive capabilities that allow this to happen. Extinction, the reduction of a certain behavior or learning previously established, refers to a very particular and interesting type of learning that has been the basis of a series of therapies to diminish non-adaptive behaviors. In recent years, the exploration of the cellular and molecular mechanisms underlying this type of learning has received increasing attention. Hebbian plasticity (the activity-dependent modification of the strength or efficacy of synaptic transmission), and homeostatic plasticity (the homeostatic regulation of plasticity) constitute processes intimately associated with memory formation and maintenance. Particularly, long-term depression (LTD) has been proposed as the underlying mechanism of extinction, while the protein phosphatase calcineurin (CaN) has been widely related to both the extinction process and LTD. In this review, we focus on the available evidence that sustains CaN modulation of LTD and its association with extinction. Beyond the classic view, we also examine the interconnection among extinction, Hebbian and homeostatic plasticity, as well as emergent evidence of the participation of kinases and long-term potentiation (LTP) on extinction learning, highlighting the importance of the balance between kinases and phosphatases in the expression of extinction. Finally, we also integrate data that shows the association between extinction and less-studied phenomena, such as synaptic silencing and engram formation that open new perspectives in the field.

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Chronic neuronal excitation leads to homeostatic suppression of structural long-term potentiation

10.1101/2021.03.16.435575 ◽

2021 ◽

Author(s):

Hiromi H Ueda ◽

Aiko Sato ◽

Maki Onda ◽

Hideji Murakoshi

Keyword(s):

Synaptic Plasticity ◽

Molecular Mechanisms ◽

Long Term Potentiation ◽

Homeostatic Plasticity ◽

Ca1 Neurons ◽

Downstream Signaling ◽

Neuronal Excitation ◽

Term Potentiation ◽

Hippocampal Ca1

Synaptic plasticity is long-lasting changes in synaptic currents and structure. When neurons are exposed to signals that induce aberrant neuronal excitation, they increase the threshold for the induction of synaptic plasticity, called homeostatic plasticity. To further understand the homeostatic regulation of synaptic plasticity and its molecular mechanisms, we investigated glutamate uncaging/photoactivatable (pa)CaMKII-dependent sLTP induction in hippocampal CA1 neurons after chronic neuronal excitation by GABAA receptor antagonists. The neuronal excitation suppressed the glutamate uncaging-evoked Ca2+ influx and failed to induce sLTP. Single-spine optogenetic stimulation using paCaMKII also failed to induce sLTP, suggesting that CaMKII downstream signaling is impaired in response to chronic neuronal excitation. Furthermore, while the inhibition of Ca2+ influx was protein synthesis-independent, paCaMKII-induced sLTP depended on it. Our findings demonstrate that chronic neuronal excitation suppresses sLTP in two independent ways (i.e., the inhibitions of Ca2+ influx and CaMKII downstream signaling), which may contribute to the robust neuronal protection in excitable environments.

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Molecular mechanisms of synaptic consolidation during sleep: BDNF function and dendritic protein synthesis

Behavioral and Brain Sciences ◽

10.1017/s0140525x05230029 ◽

2005 ◽

Vol 28 (1) ◽

pp. 65-66

Author(s):

Clive R. Bramham

Keyword(s):

Memory Consolidation ◽

Molecular Mechanisms ◽

Long Term Potentiation ◽

Term Potentiation ◽

Dendritic Protein Synthesis ◽

Mechanisms Of Memory ◽

Activity Dependent ◽

Specific Contribution

Insights into the role of sleep in the molecular mechanisms of memory consolidation may come from studies of activity-dependent synaptic plasticity, such as long-term potentiation (LTP). This commentary posits a specific contribution of sleep to LTP stabilization, in which mRNA transported to dendrites during wakefulness is translated during sleep. Brain-derived neurotrophic factor may drive the translation of newly transported and resident mRNA.

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GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2013.0141 ◽

2014 ◽

Vol 369 (1633) ◽

pp. 20130141 ◽

Cited By ~ 36

Author(s):

Oliver Hardt ◽

Karim Nader ◽

Yu-Tian Wang

Keyword(s):

Ampa Receptors ◽

Long Term Potentiation ◽

Homeostatic Plasticity ◽

Molecular Processes ◽

Short Term ◽

Receptor Endocytosis ◽

Term Potentiation ◽

Short And Long Term ◽

Activity Dependent

The molecular processes involved in establishing long-term potentiation (LTP) have been characterized well, but the decay of early and late LTP (E-LTP and L-LTP) is poorly understood. We review recent advances in describing the mechanisms involved in maintaining LTP and homeostatic plasticity. We discuss how these phenomena could relate to processes that might underpin the loss of synaptic potentiation over time, and how they might contribute to the forgetting of short-term and long-term memories. We propose that homeostatic downscaling mediates the loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP, while both processes require the activity-dependent removal of postsynaptic GluA2-containing AMPA receptors.

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Homeostatic plasticity induced by brief activity deprivation enhances long-term potentiation in the mature rat hippocampus

Journal of Neurophysiology ◽

10.1152/jn.00058.2014 ◽

2014 ◽

Vol 112 (11) ◽

pp. 3012-3022 ◽

Cited By ~ 16

Author(s):

A. Félix-Oliveira ◽

R. B. Dias ◽

M. Colino-Oliveira ◽

D. M. Rombo ◽

A. M. Sebastião

Keyword(s):

Synaptic Transmission ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Receptor Activation ◽

Relative Strength ◽

Homeostatic Plasticity ◽

Hebbian Plasticity ◽

Term Potentiation ◽

Acute Hippocampal Slices

Different forms of plasticity occur concomitantly in the nervous system. Whereas homeostatic plasticity monitors and maintains neuronal activity within a functional range, Hebbian changes such as long-term potentiation (LTP) modify the relative strength of specific synapses after discrete changes in activity and are thought to provide the cellular basis for learning and memory. Here, we assessed whether homeostatic plasticity could influence subsequent LTP in acute hippocampal slices that had been briefly deprived of activity by blocking action potential generation and N-methyl-d-aspartate (NMDA) receptor activation for 3 h. Activity deprivation enhanced the frequency and the amplitude of spontaneous miniature excitatory postsynaptic currents and enhanced basal synaptic transmission in the absence of significant changes in intrinsic excitability. Changes in the threshold for Hebbian plasticity were evaluated by inducing LTP with stimulation protocols of increasing strength. We found that activity-deprived slices consistently showed higher LTP magnitude compared with control conditions even when using subthreshold theta-burst stimulation. Enhanced LTP in activity-deprived slices was also observed when picrotoxin was used to prevent the modulation of GABAergic transmission. Finally, we observed that consecutive LTP inductions attained a higher magnitude of facilitation in activity-deprived slices, suggesting that the homeostatic plasticity mechanisms triggered by a brief period of neuronal silencing can both lower the threshold and raise the ceiling for Hebbian modifications. We conclude that even brief periods of altered activity are able to shape subsequent synaptic transmission and Hebbian plasticity in fully developed hippocampal circuits.

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Retrograde Signaling in the Development and Modification of Synapses

Physiological Reviews ◽

10.1152/physrev.1998.78.1.143 ◽

1998 ◽

Vol 78 (1) ◽

pp. 143-170 ◽

Cited By ~ 154

Author(s):

REIKO MAKI FITZSIMONDS ◽

MU-MING POO

Keyword(s):

Long Term Potentiation ◽

Retrograde Signaling ◽

Presynaptic Neuron ◽

Term Potentiation ◽

Postsynaptic Cell ◽

Membrane Bound ◽

Dependent Modification ◽

And Function ◽

Activity Dependent

Fitzsimonds, Reiko Maki, and Mu-ming Poo. Retrograde Signaling in the Development and Modification of Synapses. Physiol. Rev. 78: 143–170, 1998. — Retrograde signaling from the postsynaptic cell to the presynaptic neuron is essential for the development, maintenance, and activity-dependent modification of synaptic connections. This review covers various forms of retrograde interactions at developing and mature synapses. First, we discuss evidence for early retrograde inductive events during synaptogenesis and how maturation of presynaptic structure and function is affected by signals from the postsynaptic cell. Second, we review the evidence that retrograde interactions are involved in activity-dependent synapse competition and elimination in developing nervous systems and in long-term potentiation and depression at mature synapses. Third, we review evidence for various forms of retrograde signaling via membrane-permeant factors, secreted factors, and membrane-bound factors. Finally, we discuss the evidence and physiological implications of the long-range propagation of retrograde signals to the cell body and other parts of the presynaptic neuron.

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Clustered plasticity in Long-Term Potentiation: How strong synapses persist to maintain long-term memory

Neuroforum ◽

10.1515/nf-2018-a006 ◽

2018 ◽

Vol 24 (3) ◽

pp. A127-A132

Author(s):

Marina Mikhaylova ◽

Michael R. Kreutz

Keyword(s):

Molecular Mechanisms ◽

Synaptic Weight ◽

Long Term Potentiation ◽

Long Term Memory ◽

Term Memory ◽

Term Potentiation ◽

Associated Functions ◽

Time Periods ◽

Activity Dependent

Abstract The storage of memory requires at least in part maintenance of long-term potentiation (LTP) in dendritic spine synapses. Neighboring synapses are frequently arranged into functional clusters. At present, it is still unclear how these clusters evolve, why they are stable for longer time periods and how spines interact within a cluster. In this review, we will provide an overview of current concepts of clustered plasticity and we will discuss cellular as well as molecular mechanisms that might be relevant for spine stability and associated functions in the context of LTP. We will propose that dynamics of initially formed clusters depend on compartmentalization of dendrites and that activity-dependent gene expression kicks in to preserve differences in synaptic weight. We will discuss how mechanisms of synaptic tagging, the presence of secretory organelles in dendrites and the incorporation of synaptic scaling factors that are encoded by immediate early genes interact to preserve clustered plasticity.

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The Vertical Lobe of Cephalopods

The Oxford Handbook of Invertebrate Neurobiology ◽

10.1093/oxfordhb/9780190456757.013.29 ◽

2017 ◽

pp. 558-574 ◽

Cited By ~ 1

Author(s):

Ana Turchetti-Maia ◽

Tal Shomrat ◽

Binyamin Hochner

Keyword(s):

Complex Networks ◽

Long Term Potentiation ◽

Learning Networks ◽

Neuronal Circuitry ◽

Cellular Processes ◽

Term Potentiation ◽

Matrix Organization ◽

Activity Dependent ◽

Similar Organization

We show that the cephalopod vertical lobe (VL) is a promising system for assessing the function and organization of the neuronal circuitry mediating complex learning and memory behavior. Studies in octopus and cuttlefish VL networks suggest an independent evolutionary convergence into a matrix organization of a divergence-convergence (“fan-out fan-in”) network with activity-dependent long-term plasticity mechanisms. These studies also show, however, that the properties of the neurons, neurotransmitters, neuromodulators, and mechanisms of induction and maintenance of long-term potentiation are different from those evolved in vertebrates and other invertebrates, and even highly variable among these two cephalopod species. This suggests that complex networks may have evolved independently multiple times and that, even though memory and learning networks share similar organization and cellular processes, there are many molecular ways of constructing them.

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