Homeostatic Plasticity Scales Dendritic Spine Volumes and Changes the Threshold and Specificity of Hebbian Plasticity

Hobbiss, Anna Felicity; Ramiro-Cortés, Yazmín; Israely, Inbal

doi:10.1016/j.isci.2018.09.015

Cited by 36 publications

(41 citation statements)

References 56 publications

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“…39,40 Several forms of homeostatic plasticity have been identified and include mechanisms that regulate neuronal excitability, stabilize total synaptic strength, and influence the rate and extent of synapse formation. 41 These forms of homeostatic plasticity are likely to complement Hebbian mechanisms to allow the modification of neuronal networks selectively. 41 In essence, the whole synaptic population is equally affected, such that the overall sum of synaptic strengthening and therefore activity of a neuron is changed but the relative weighed differences between synapses is preserved: the computational and storage capacity of the network is not compromised and homeostatic plasticity will not be in conflict with or erase the information set by Hebbian plasticity.…”

Section: Synaptic Plasticitymentioning

confidence: 99%

“…41 These forms of homeostatic plasticity are likely to complement Hebbian mechanisms to allow the modification of neuronal networks selectively. 41 In essence, the whole synaptic population is equally affected, such that the overall sum of synaptic strengthening and therefore activity of a neuron is changed but the relative weighed differences between synapses is preserved: the computational and storage capacity of the network is not compromised and homeostatic plasticity will not be in conflict with or erase the information set by Hebbian plasticity. 41 The Aged Glutamatergic Synapse According to the World Health Organization (WHO), by 2020, the number of people aged 60 years and older will outnumber children younger than 5 years.…”

Section: Synaptic Plasticitymentioning

confidence: 99%

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Novel Players in the Aging Synapse: Impact on Cognition

Temido‐Ferreira

Coelho

Pousinha

et al. 2019

Journal of Caffeine and Adenosine Research

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While neuronal loss has long been considered as the main contributor to age-related cognitive decline, these alterations are currently attributed to gradual synaptic dysfunction driven by calcium dyshomeostasis and alterations in ionotropic/metabotropic receptors. Given the key role of the hippocampus in encoding, storage, and retrieval of memory, the morpho-and electrophysiological alterations that occur in the major synapse of this network-the glutamatergic-deserve special attention. We guide you through the hippocampal anatomy, circuitry, and function in physiological context and focus on alterations in neuronal morphology, calcium dynamics, and plasticity induced by aging and Alzheimer's disease (AD). We provide state-of-the art knowledge on glutamatergic transmission and discuss implications of these novel players for intervention. A link between regular consumption of caffeine-an adenosine receptor blocker-to decreased risk of AD in humans is well established, while the mechanisms responsible have only now been uncovered. We review compelling evidence from humans and animal models that implicate adenosine A 2A receptors (A 2A R) upsurge as a crucial mediator of age-related synaptic dysfunction. The relevance of this mechanism in patients was very recently demonstrated in the form of a significant association of the A 2A R-encoding gene with hippocampal volume (synaptic loss) in mild cognitive impairment and AD. Novel pathways implicate A 2A R in the control of mGluR5-dependent NMDAR activation and subsequent Ca 2+ dysfunction upon aging. The nature of this receptor makes it particularly suited for long-term therapies, as an alternative for regulating aberrant mGluR5/NMDAR signaling in aging and disease, without disrupting their crucial constitutive activity.

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Section: Synaptic Plasticitymentioning

confidence: 99%

Section: Synaptic Plasticitymentioning

confidence: 99%

Novel Players in the Aging Synapse: Impact on Cognition

Temido‐Ferreira

Coelho

Pousinha

et al. 2019

Journal of Caffeine and Adenosine Research

View full text Add to dashboard Cite

show abstract

“…To ensure that no significant biological remodeling occurred either at the dendrite or spines over the course of the in-vitro experiment we acutely added tetrodotoxin (TTX) into the artificial cerebrospinal fluid (ACSF) used to perfuse the neuron during the imaging session. It has been shown that application of TTX changes spine volumes only upon prolonged application 40 . We subsequently analyzed spines to investigate if the segmentation performance and resulting IFI volumes were sensitive to different levels of fluorescence.…”

Section: Fluorescence Intensity Invariant Performance In Spine Segmenmentioning

confidence: 99%

SpineS: An interactive time-series analysis software for dendritic spines

Argunşah

Erdil

Ghani

et al. 2020

Preprint

Self Cite

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Live fluorescence imaging has shown the dynamic nature of dendritic spines, with changes in shape occurring both during development and in response to activity. The structure of a dendritic spine positively correlates with its functional efficacy. Learning and memory studies have shown that great deal of the information stored by a neuron is contained in the synapses. High precision tracking of synaptic structures can give hints about the dynamic nature of memory and help us to understand how memories evolve both in biological and artificial neural networks. Experiments that aim to investigate the dynamics behind the structural changes of dendritic spines require the collection and analysis of large time-series datasets. In this paper, we present an open-source software called SpineS for the automatic longitudinal structural analysis of dendritic spines with additional features for manual intervention to ensure optimal analysis. Our extensive experimental analyses on multiple datasets demonstrate that SpineS can achieve a high-level performance on samples collected both by two-photon and confocal imaging systems.

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“…This form of plasticity is inherently unstable, as a small change in synaptic strength can promote further change in the same direction, and this positive reinforcement can drive synaptic efficacies to either saturate or reduce to a minimum (Abbott & Nelson, ; Honnuraiah & Narayanan, ; Hobbiss et al . ). It has long been recognized that Hebbian rules need to be supplemented with additional stabilizing mechanisms to curb runaway plasticity and support stable yet flexible neural circuits (Abbott & Nelson, ; Zenke & Gerstner, ; Keck et al .…”

Section: Introductionmentioning

confidence: 97%

Intracellular calcium stores mediate metaplasticity at hippocampal dendritic spines

Mahajan

Nadkarni

2019

The Journal of Physiology

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Key points Calcium (Ca2+) entry mediated by NMDA receptors is considered central to the induction of activity‐dependent synaptic plasticity in hippocampal area CA1; this description does not, however, take into account the potential contribution of endoplasmic reticulum (ER) Ca2+ stores. The ER has a heterogeneous distribution in CA1 dendritic spines, and may introduce localized functional differences in Ca2+ signalling between synapses, as suggested by experiments on metabotropic receptor‐dependent long‐term depression. A physiologically detailed computational model of Ca2+ dynamics at a CA3–CA1 excitatory synapse characterizes the contribution of spine ER via metabotropic signalling during plasticity induction protocols. ER Ca2+ release via IP3 receptors modulates NMDA receptor‐dependent plasticity in a graded manner, to selectively promote synaptic depression with relatively diminished effect on LTP induction; this may temper further strengthening at the stronger synapses which are preferentially associated with ER‐containing spines. Acquisition of spine ER may thus represent a local, biophysically plausible ‘metaplastic switch’ at potentiated CA1 synapses, contributing to the plasticity–stability balance in neural circuits. Abstract Long‐term plasticity mediated by NMDA receptors supports input‐specific, Hebbian forms of learning at excitatory CA3–CA1 connections in the hippocampus. There exists an additional layer of stabilizing mechanisms that act globally as well as locally over multiple time scales to ensure that plasticity occurs in a constrained manner. Here, we investigated the role of calcium (Ca2+) stores associated with the endoplasmic reticulum (ER) in the local regulation of plasticity at individual CA1 synapses. Our study was spurred by (1) the curious observation that ER is sparsely distributed in dendritic spines, but over‐represented in larger spines that are likely to have undergone activity‐dependent strengthening, and (2) evidence suggesting that ER motility at synapses can be rapid, and accompany activity‐regulated spine remodelling. We constructed a physiologically realistic computational model of an ER‐bearing CA1 spine, and examined how IP3‐sensitive Ca2+ stores affect spine Ca2+ dynamics during activity patterns mimicking the induction of long‐term potentiation and long‐term depression (LTD). Our results suggest that the presence of ER modulates NMDA receptor‐dependent plasticity in a graded manner that selectively enhances LTD induction. We propose that ER may locally tune Ca2+‐based plasticity, providing a braking mechanism to mitigate runaway strengthening at potentiated synapses. Our study provides a biophysically accurate description of postsynaptic Ca2+ regulation, and suggests that ER in the spine may promote the re‐use of hippocampal synapses with saturated strengths.

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Homeostatic Plasticity Scales Dendritic Spine Volumes and Changes the Threshold and Specificity of Hebbian Plasticity

Cited by 36 publications

References 56 publications

Novel Players in the Aging Synapse: Impact on Cognition

Novel Players in the Aging Synapse: Impact on Cognition

SpineS: An interactive time-series analysis software for dendritic spines

Intracellular calcium stores mediate metaplasticity at hippocampal dendritic spines

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