Faculty Opinions recommendation of Transport of a kinesin-cargo pair along microtubules into dendritic spines undergoing synaptic plasticity.

Actin turnover in dendritic spines influences spine development, morphology, and plasticity, with functional consequences on learning and memory formation. In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways. Using in vitro models of neuronal plasticity, such as glycine-induced chemical long-term potentiation (LTP), known to evoke synaptic plasticity, or long-term depolarization block by KCl, leading to homeostatic morphological changes, we show that actin stabilization needed for the enlargement of dendritic spines is dependent on PKD activity. Consequently, impaired PKD functions attenuate activity-dependent changes in hippocampal dendritic spines, including LTP formation, cause morphological alterations in vivo, and have deleterious consequences on spatial memory formation. We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulating actin stability in dendritic spines.

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Biophysics of Biochemical Signaling in Dendritic Spines: Implications in Synaptic Plasticity

Biophysical Journal ◽

10.1016/j.bpj.2017.07.029 ◽

2017 ◽

Vol 113 (10) ◽

pp. 2152-2159 ◽

Cited By ~ 37

Author(s):

Ryohei Yasuda

Keyword(s):

Synaptic Plasticity ◽

Dendritic Spines

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Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

Biological Chemistry ◽

10.1515/hsz-2019-0110 ◽

2019 ◽

Vol 400 (9) ◽

pp. 1129-1139 ◽

Cited By ~ 2

Author(s):

Iryna Hlushchenko ◽

Pirta Hotulainen

Keyword(s):

Synaptic Plasticity ◽

Dendritic Spines ◽

Hippocampal Neurons ◽

Long Term Potentiation ◽

Excitatory Synapses ◽

Signal Molecule ◽

Brain Functions ◽

Dendritic Shaft ◽

Term Potentiation

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

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Metabolic constraints on synaptic learning and memory

Journal of Neurophysiology ◽

10.1152/jn.00092.2019 ◽

2019 ◽

Vol 122 (4) ◽

pp. 1473-1490 ◽

Cited By ~ 2

Author(s):

Jan Karbowski

Keyword(s):

Synaptic Plasticity ◽

Metabolic Rate ◽

Protein Phosphorylation ◽

Learning And Memory ◽

Dendritic Spines ◽

Energy Cost ◽

Memory Trace ◽

Metabolic Energy ◽

Cascade Models ◽

New Learning

Dendritic spines, the carriers of long-term memory, occupy a small fraction of cortical space, and yet they are the major consumers of brain metabolic energy. What fraction of this energy goes for synaptic plasticity, correlated with learning and memory? It is estimated here based on neurophysiological and proteomic data for rat brain that, depending on the level of protein phosphorylation, the energy cost of synaptic plasticity constitutes a small fraction of the energy used for fast excitatory synaptic transmission, typically 4.0–11.2%. Next, this study analyzes a metabolic cost of new learning and its memory trace in relation to the cost of prior memories, using a class of cascade models of synaptic plasticity. It is argued that these models must contain bidirectional cyclic motifs, related to protein phosphorylation, to be compatible with basic thermodynamic principles. For most investigated parameters longer memories generally require proportionally more energy to store. The exceptions are the parameters controlling the speed of molecular transitions (e.g., ATP-driven phosphorylation rate), for which memory lifetime per invested energy can increase progressively for longer memories. Furthermore, in general, a memory trace decouples dynamically from a corresponding synaptic metabolic rate such that the energy expended on new learning and its memory trace constitutes in most cases only a small fraction of the baseline energy associated with prior memories. Taken together, these empirical and theoretical results suggest a metabolic efficiency of synaptically stored information. NEW & NOTEWORTHY Learning and memory involve a sequence of molecular events in dendritic spines called synaptic plasticity. These events are physical in nature and require energy, which has to be supplied by ATP molecules. However, our knowledge of the energetics of these processes is very poor. This study estimates the empirical energy cost of synaptic plasticity and considers theoretically a metabolic rate of learning and its memory trace in a class of cascade models of synaptic plasticity.

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Differential aberrant structural synaptic plasticity in axons and dendrites ahead of their degeneration in tauopathy

10.1101/2020.04.29.067629 ◽

2020 ◽

Cited By ~ 2

Author(s):

Johanna S. Jackson ◽

James D. Johnson ◽

Soraya Meftah ◽

Tracey K Murray ◽

Zeshan Ahmed ◽

...

Keyword(s):

Synaptic Plasticity ◽

Disease Progression ◽

Dendritic Spines ◽

Time Course ◽

Neuronal Degeneration ◽

List Type ◽

Synapse Plasticity ◽

Synapse Density ◽

A Cell ◽

Neurite Degeneration

AbstractNeurodegeneration driven by aberrant tau is a key feature of many dementias. Pathological stages of tauopathy are characterised by reduced synapse density and altered synapse function. Furthermore, changes in synaptic plasticity have been documented in the early stages of tauopathy suggesting that they may be a driver of later pathology. However, it remains unclear if synapse plasticity is specifically linked to the degeneration of neurons. This is partly because, in progressive dementias, pathology can vary widely from cell-to-cell along the prolonged disease time-course. To overcome this variability, we have taken a longitudinal experimental approach to track individual neurons through the progression of neurodegenerative tauopathy. Using repeated in vivo 2-photon imaging in rTg4510 transgenic mice, we have measured structural plasticity of presynaptic terminaux boutons and postsynaptic spines on individual axons and dendrites over long periods of time. By following individual neurons, we have measured synapse density across the neuronal population and tracked changes in synapse turnover in each neuron. We found that tauopathy drives a reduction in density of both presynaptic and postsynaptic structures and that this is partially driven by degeneration of individual axons and dendrites that are spread widely across the disease time-course. Both synaptic loss and neuronal degeneration was ameliorated by reduction in expression of the aberrant P301L transgene, but only if that reduction was initiated early in disease progression. Notably, neurite degeneration was preceded by alterations in synapse turnover that contrasted in axons and dendrites. In dendrites destined to die, there was a dramatic loss of spines in the week immediately before degeneration. In contrast, axonal degeneration was preceded by a progressive attenuation of presynaptic turnover that started many weeks before axon disappearance. Therefore, changes in synapse plasticity are harbingers of degeneration of individual neurites that occur at differing stages of tau-driven neurodegenerative disease, suggesting a cell or neurite autonomous process. Furthermore, the links between synapse plasticity and degeneration are distinct in axonal and dendritic compartments.Key findingsTauopathy driven by tau P301L in rTg4510 mice causes a progressive decrease in density of presynaptic terminaux boutons and postsynaptic dendritic spines in cortical excitatory neurons.Longitudinal imaging of individual axons and dendrites shows that there is a huge diversity of effects at varying times in different cells.Decreases in overall synapse density are driven partly, but not exclusively, by degeneration of dendrites and axons that are distributed widely across the time-course of disease.Suppression of pathological P301L tau expression can ameliorate accumulation of tau pathology, synapse loss and neurodegeneration, but only if administered early in disease progression.Neurite degeneration is preceded by aberrant structural synaptic plasticity in a cell-specific way that is markedly different in dendrites and axons.Degeneration of dendrites is immediately preceded by dramatic loss of dendritic spines.Axonal loss is characterised by a progressive attenuation of presynaptic bouton plasticity that starts months before degeneration.

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