scholarly journals Homeostatic plasticity scales dendritic spine volumes and changes the threshold and specificity of Hebbian plasticity

2018 ◽  
Author(s):  
Anna F. Hobbiss ◽  
Yazmin Ramiro Cortés ◽  
Inbal Israely
Keyword(s):  
Hippocampal Neurons ◽  
Structural Plasticity ◽  
Long Term Potentiation ◽  
Homeostatic Plasticity ◽  
Weight Changes ◽  
Size Dependent ◽  
Hebbian Plasticity ◽  
Term Potentiation ◽  
Functional Consequences ◽  
Synaptic Learning

AbstractInformation is encoded within neural networks through synaptic weight changes. Synaptic learning rules involve a combination of rapid Hebbian plasticity with slower homeostatic synaptic plasticity (HSP) that regulates neuronal activity through global synaptic scaling. While Hebbian plasticity has been extensively investigated, much less is known about HSP. Here we investigate the structural and functional consequences of HSP at dendritic spines of mouse hippocampal neurons. We find that prolonged activity blockade induces spine growth, paralleling synaptic strength increases. Following activity blockade, glutamate uncaging-mediated long-term potentiation at single spines leads to size-dependent structural plasticity: smaller spines undergo robust growth, while larger spines remain unchanged. Moreover, we find that neighboring spines in the vicinity of the stimulated spine exhibit volume changes following HSP, indicating that plasticity has spread across a group of synapses. Overall, these findings demonstrate that Hebbian and homeostatic plasticity shape neural connectivity through coordinated structural plasticity of clustered inputs.

scholarly journals Calcineurin Participation in Hebbian and Homeostatic Plasticity Associated With Extinction

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.

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

2014 ◽  
Vol 112 (11) ◽  
pp. 3012-3022 ◽  
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.

scholarly journals Synaptic crosstalk conferred by a zone of differentially regulated Ca2+ signaling in the dendritic shaft adjoining a potentiated spine

2019 ◽  
Vol 116 (27) ◽  
pp. 13611-13620 ◽  
Author(s):  
Philip J. Dittmer ◽  
Mark L. Dell’Acqua ◽  
William A. Sather
Keyword(s):  
Hippocampal Neurons ◽  
Feedback Inhibition ◽  
Activity Patterns ◽  
Structural Plasticity ◽  
Long Term Potentiation ◽  
Channel Current ◽  
Excitatory Transmission ◽  
Postsynaptic Activity ◽  
Dendritic Shaft ◽  
Term Potentiation

Patterns of postsynaptic activity that induce long-term potentiation of fast excitatory transmission at glutamatergic synapses between hippocampal neurons cause enlargement of the dendritic spine and promote growth in spine endoplasmic reticulum (ER) content. Such postsynaptic activity patterns also impact Ca2+ signaling in the adjoining dendritic shaft, in a zone centered on the spine–shaft junction and extending ∼10–20 µm in either direction along the shaft. Comparing this specialized zone in the shaft with the dendrite in general, plasticity-inducing stimulation of a single spine causes more profound depletion of Ca2+ stores in the ER, a greater degree of interaction between stromal interaction molecule 1 (STIM1) and L-type Ca2+ channels, and thus stronger STIM1 inhibition of these channels. Here we show that the length of this zone along the dendritic axis can be approximately doubled through the neuromodulatory action of β-adrenergic receptors (βARs). The mechanism of βAR enlargement of the zone arises from protein kinase A-mediated enhancement of L-type Ca2+ current, which in turn lowers [Ca2+]ER through ryanodine receptor-dependent Ca2+-induced Ca2+ release and activates STIM1 feedback inhibition of L-type Ca2+ channels. An important function of this dendritic zone is to support crosstalk between spines along its length such that spines neighboring a strongly stimulated spine are enabled to undergo structural plasticity in response to stimulation that would otherwise be subthreshold for spine structural plasticity. This form of crosstalk requires L-type Ca2+ channel current to activate STIM1, and βAR activity extends the range along the shaft over which such spine-to-spine communication can occur.

scholarly journals A role for BDNF- and NMDAR-induced lysosomal recruitment of mTORC1 in the regulation of neuronal mTORC1 activity

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Dany Khamsing ◽  
Solène Lebrun ◽  
Isabelle Fanget ◽  
Nathanaël Larochette ◽  
Christophe Tourain ◽  
...  
Keyword(s):  
Amino Acids ◽  
Nmda Receptors ◽  
Hippocampal Neurons ◽  
De Novo ◽  
Long Term Potentiation ◽  
Activation Mechanism ◽  
Functional Link ◽  
Term Potentiation ◽  
Endocytic Compartments ◽  
Mtorc1 Activation

AbstractMemory and long term potentiation require de novo protein synthesis. A key regulator of this process is mTORC1, a complex comprising the mTOR kinase. Growth factors activate mTORC1 via a pathway involving PI3-kinase, Akt, the TSC complex and the GTPase Rheb. In non-neuronal cells, translocation of mTORC1 to late endocytic compartments (LEs), where Rheb is enriched, is triggered by amino acids. However, the regulation of mTORC1 in neurons remains unclear. In mouse hippocampal neurons, we observed that BDNF and treatments activating NMDA receptors trigger a robust increase in mTORC1 activity. NMDA receptors activation induced a significant recruitment of mTOR onto lysosomes even in the absence of external amino acids, whereas mTORC1 was evenly distributed in neurons under resting conditions. NMDA receptor-induced mTOR translocation to LEs was partly dependent on the BDNF receptor TrkB, suggesting that BDNF contributes to the effect of NMDA receptors on mTORC1 translocation. In addition, the combination of Rheb overexpression and artificial mTORC1 targeting to LEs by means of a modified component of mTORC1 fused with a LE-targeting motif strongly activated mTOR. To gain spatial and temporal control over mTOR localization, we designed an optogenetic module based on light-sensitive dimerizers able to recruit mTOR on LEs. In cells expressing this optogenetic tool, mTOR was translocated to LEs upon photoactivation. In the absence of growth factor, this was not sufficient to activate mTORC1. In contrast, mTORC1 was potently activated by a combination of BDNF and photoactivation. The data demonstrate that two important triggers of synaptic plasticity, BDNF and NMDA receptors, synergistically power the two arms of the mTORC1 activation mechanism, i.e., mTORC1 translocation to LEs and Rheb activation. Moreover, they unmask a functional link between NMDA receptors and mTORC1 that could underlie the changes in the synaptic proteome associated with long-lasting changes in synaptic strength.

scholarly journals Silencing-Induced Metaplasticity in Hippocampal Cultured Neurons

2008 ◽  
Vol 100 (2) ◽  
pp. 690-697 ◽  
Author(s):  
Irina V. Sokolova ◽  
Istvan Mody
Keyword(s):  
Hippocampal Neurons ◽  
Channel Blocker ◽  
Recovery Period ◽  
Long Term Potentiation ◽  
Homeostatic Plasticity ◽  
Membrane Properties ◽  
Postsynaptic Currents ◽  
Short Period ◽  
Spiking Activity

Silencing-induced homeostatic plasticity is usually expressed as a change in the amplitude or the frequency of miniature postsynaptic currents. Here we report that, prolonged (∼24 h) silencing of mature (20–22 days in vitro) cultured hippocampal neurons using the voltage-gated sodium channel blocker tetrodotoxin (TTX) produced no effects on the amplitude or frequency of the miniature excitatory postsynaptic currents (mEPSCs). However, the silencing changed the intrinsic membrane properties of the neurons, resulting in an increased excitability and rate of action potentials firing upon TTX washout. Allowing neurons to recover in TTX-free recording solution for a short period of time after the silencing resulted in potentiation of mEPSC amplitudes. This form of activity-dependent potentiation is different from classical long-term potentiation, as similar potentiation was not seen in nonsilenced neurons treated with bicuculline to raise their spiking activity to the same level displayed by the silenced neurons during TTX washout. Also, the potentiation of mEPSC amplitudes after the recovery period was not affected by the N-methyl-d-aspartate receptor blocker d-2-amino-5-phosponopentanoic acid or by the calcium/calmodulin-dependent kinase II (CaMKII) inhibitor KN-62 but was abolished by the L-type calcium channel blocker nifedipine. We thus conclude that the potentiation of mEPSC amplitudes following brief recovery of spiking activity in chronically silenced neurons represents a novel form of metaplasticity that differs from the conventional models of homeostatic synaptic plasticity.

scholarly journals Selective increase of functional network connectivity in Arc-positive neuronal engrams after long-term potentiation

2020 ◽  
Author(s):  
Yuheng Jiang ◽  
Antonius M.J. VanDongen
Keyword(s):  
Functional Connectivity ◽  
Hippocampal Neurons ◽  
Network Effects ◽  
Network Connectivity ◽  
Long Term Potentiation ◽  
Early Gene ◽  
Memory Traces ◽  
Term Potentiation ◽  
Memory Engram

ABSTRACTNew tools in optogenetics and molecular biology have culminated in recent studies which mark immediate-early gene (IEG)-expressing neurons as memory traces or engrams. Although the activity-dependent expression of IEGs has been successfully utilised to label memory traces, their roles in engram specification is incompletely understood. Outstanding questions remain as to whether expression of IEGs can interplay with network properties such as functional connectivity and also if neurons expressing different IEGs are functionally distinct. We investigated the expression of Arc and c-Fos, two commonly utilised IEGs in memory engram specification, in cultured hippocampal neurons. After pharmacological induction of long-term potentiation (LTP) in the network, we noted an emergent network property of refinement in functional connectivity between neurons, characterized by a global down-regulation of network connectivity, together with strengthening of specific connections. Subsequently, we show that Arc expression correlates with the effects of network refinement, with Arc-positive neurons being selectively strengthened. Arc positive neurons were also found to be located in closer physical proximity to each other in the network. While the expression pattern of IEGs c-Fos and Arc strongly overlaps, Arc was more selectively expressed than c-Fos. These IEGs also act together in coding information about connection strength pruning. These results demonstrate important links between IEG expression and network connectivity, which serve to bridge the gap between cellular correlates and network effects in learning and memory.

scholarly journals Aβ-induced synaptic injury is mediated by presynaptic expression of amyloid precursor protein (APP) in hippocampal neurons

2020 ◽  
Author(s):  
Elena Vicario-Orri ◽  
Kensaku Kasuga ◽  
Sheue-Houy Tyan ◽  
Karen Chiang ◽  
Silvia Viana da Silva ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Hippocampal Neurons ◽  
Kinase Inhibitors ◽  
Light And Electron Microscopy ◽  
Long Term Potentiation ◽  
Precursor Protein ◽  
Plaque Deposition ◽  
Fyn Kinase ◽  
Term Potentiation ◽  
Ca3 Neurons

ABSTRACTThe patterns of Aβ-induced synaptic injury were examined after targeting of the amyloid precursor protein (APP) preferentially to either CA1 or CA3 neurons using Cre-lox technology combined with tetracycline-regulated expression. Both CA1- and CA3-APP-expressing transgenic mouse lines exhibited reduction in long-term potentiation (LTP) only when APP was expressed in neurons presynaptic to the recording site, whereas LTP remained comparable to wild-type mice when APP was expressed in postsynaptic neurons. As quantified by both light and electron microscopy, this orientation-specific impairment in synaptic plasticity was mirrored by synaptic loss in regions receiving axonal inputs from neurons expressing APP. Furthermore, A(plaque deposition also occurred only in the postsynaptic axonal fields of APP-expressing neurons. These deficits were reversed not only with doxycycline to inhibit APP expression but also with γ-secretase and Fyn kinase inhibitors, supporting the interpretation that the observed synaptic injury was mediated by Aβ. Taken together, these results demonstrate that APP/Aβ-induced synaptic toxicity is preferentially initiated by signaling of presynaptically expressed APP to the postsynaptic compartment.

scholarly journals Microtubule‐associated protein 2 mediates induction of long‐term potentiation in hippocampal neurons

2020 ◽  
Vol 34 (5) ◽  
pp. 6965-6983 ◽  
Author(s):  
Yoonju Kim ◽  
You‐Na Jang ◽  
Ji‐Young Kim ◽  
Nari Kim ◽  
Seulgi Noh ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Term Potentiation

scholarly journals Age-Related Cognitive Impairment: Role of Reduced Synaptobrevin-2 Levels in Deficits of Memory and Synaptic Plasticity

2019 ◽  
Vol 75 (9) ◽  
pp. 1624-1632 ◽  
Author(s):  
Albert Orock ◽  
Sreemathi Logan ◽  
Ferenc Deak
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Receptor Protein ◽  
Protein Levels ◽  
Ca1 Region ◽  
Age Related ◽  
Term Potentiation

AbstractCognitive impairment in the aging population is quickly becoming a health care priority, for which currently no disease-modifying treatment is available. Multiple domains of cognition decline with age even in the absence of neurodegenerative diseases. The cellular and molecular changes leading to cognitive decline with age remain elusive. Synaptobrevin-2 (Syb2), the major vesicular SNAP receptor protein, highly expressed in the cerebral cortex and hippocampus, is essential for synaptic transmission. We have analyzed Syb2 protein levels in mice and found a decrease with age. To investigate the functional consequences of lower Syb2 expression, we have used adult Syb2 heterozygous mice (Syb2+/−) with reduced Syb2 levels. This allowed us to mimic the age-related decrease of Syb2 in the brain in order to selectively test its effects on learning and memory. Our results show that Syb2+/− animals have impaired learning and memory skills and they perform worse with age in the radial arm water maze assay. Syb2+/− hippocampal neurons have reduced synaptic plasticity with reduced release probability and impaired long-term potentiation in the CA1 region. Syb2+/− neurons also have lower vesicular release rates when compared to WT controls. These results indicate that reduced Syb2 expression with age is sufficient to cause cognitive impairment.

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