scholarly journals Actin in dendritic spines: connecting dynamics to function

2010 ◽  
Vol 189 (4) ◽  
pp. 619-629 ◽  
Author(s):  
Pirta Hotulainen ◽  
Casper C. Hoogenraad
Keyword(s):  
Dendritic Spines ◽  
Synaptic Activity ◽  
Actin Dynamics ◽  
Excitatory Synapses ◽  
Synaptic Connections ◽  
Neuronal Dendrites ◽  
Brain Changes ◽  
Processing And Storage ◽  
And Storage ◽  
The Brain

Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses and are major sites of information processing and storage in the brain. Changes in the shape and size of dendritic spines are correlated with the strength of excitatory synaptic connections and heavily depend on remodeling of its underlying actin cytoskeleton. Emerging evidence suggests that most signaling pathways linking synaptic activity to spine morphology influence local actin dynamics. Therefore, specific mechanisms of actin regulation are integral to the formation, maturation, and plasticity of dendritic spines and to learning and memory.

Development and Regulation of Dendritic Spine Synapses

Physiology ◽  
2006 ◽  
Vol 21 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Barbara Calabrese ◽  
Margaret S. Wilson ◽  
Shelley Halpain
Keyword(s):  
Synaptic Transmission ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Excitatory Synapses ◽  
Dense Array ◽  
Complex Dynamic ◽  
Neuronal Dendrites ◽  
Spine Abnormalities ◽  
Dynamic Structures ◽  
The Brain

Dendritic spines are small protrusions from neuronal dendrites that form the postsynaptic component of most excitatory synapses in the brain. They play critical roles in synaptic transmission and plasticity. Recent advances in imaging and molecular technologies reveal that spines are complex, dynamic structures that contain a dense array of cytoskeletal, transmembrane, and scaffolding molecules. Several neurological and psychiatric disorders exhibit dendritic spine abnormalities.

scholarly journals Activity-dependent expression of reporter proteins at dendritic spines for synaptic activity mapping and optogenetic stimulation

2016 ◽  
Author(s):  
Francesco Gobbo ◽  
Laura Marchetti ◽  
Claudia Alia ◽  
Stefano Luin ◽  
Antonino Cattaneo
Keyword(s):  
Dendritic Spines ◽  
Cognitive Disorders ◽  
Synaptic Activity ◽  
Regulatory Sequences ◽  
Synaptic Connections ◽  
Optogenetic Stimulation ◽  
Reporter Proteins ◽  
Activity Dependent ◽  
The Brain ◽  
Spine Number

Increasing evidence points to the importance of dendritic spines in the formation and allocation of memories, and alterations of spine number and physiology are associated to memory and cognitive disorders. Synaptic connections and pathways constitute the physical substrate that conveys information in the brain, and different combinations of active synaptic connections are believed to be responsible for the encoding of specific memories. In addition, modifications of the activity of such subsets of synapses are believed to be crucial for memory establishment, but a way to directly test this hypothesis, by selectively controlling the activity of potentiated spines, is currently lagging behind. Therefore it would be important to develop methods to tag active synapses for mapping functionally active connections and to selectively stimulate or interfere with active synapses. Here we introduce an approach to express light-sensitive membrane channels at synapses in an activity-dependent way by means of RNA and protein regulatory sequences. This approach is based on the local expression of reporter proteins, including optogenetic probes, at activated synapses and will allow the mapping of previously active synapses and the re-activation of the neuron only at these sites. This will allow extending the investigation of memory processes beyond the current neuron tagging technologies, whose resolution is limited at the cellular scale. Thus, it will be possible to unveil and recall the synaptic engram out of the global set of synapses.

Defective actin dynamics in dendritic spines: cause or consequence of age-induced cognitive decline?

2016 ◽  
Vol 397 (3) ◽  
pp. 223-229 ◽  
Author(s):  
Till Georg Alexander Mack ◽  
Patricia Kreis ◽  
Britta Johanna Eickholt
Keyword(s):  
Dendritic Spines ◽  
Neuronal Excitability ◽  
Replicative Senescence ◽  
Morphological Changes ◽  
Actin Dynamics ◽  
Cellular Processes ◽  
Filament Dynamics ◽  
Neuronal Soma ◽  
Deteriorating Process ◽  
The Brain

Abstract Ageing is a complex deteriorating process that coincides with changes in metabolism, replicative senescence, increased resistance to apoptosis, as well as progressive mitochondria dysfunction that lead to an increase production and accumulation of reactive oxygen species (ROS). Although controversy on the paradigm of the oxidative damage theory of ageing exists, persuasive studies in Caenorhabditis elegans and yeast have demonstrated that manipulation of ROS can modify the process of ageing and influences the damage of proteins, lipids and DNA. In neurons, ageing impacts on the intrinsic neuronal excitability, it decreases the size of neuronal soma and induces the loss of dendrites and dendritic spines. The actin cytoskeleton is an abundant and broadly expressed system that plays critical functions in many cellular processes ranging from cell motility to controlling cell shape and polarity. It is thus hardly surprising that the expression and the function of actin in neurons is crucial for the morphological changes that occur in the brain throughout life. We propose that alterations in actin filament dynamics in dendritic spines may be one of the key events contributing to the initial phases of ageing in the brain.

scholarly journals More than a mere supply of monomers: G-Actin pools regulate actin dynamics in dendritic spines

2017 ◽  
Vol 216 (8) ◽  
pp. 2255-2257 ◽  
Author(s):  
Katalin Schlett
Keyword(s):  
Plasma Membrane ◽  
Dendritic Spines ◽  
Actin Polymerization ◽  
Synaptic Activity ◽  
Actin Dynamics ◽  
Actin Monomer ◽  
Cell Biol ◽  
Local Enrichment

Synaptic activity reshapes the morphology of dendritic spines via regulating F-actin arborization. In this issue, Lei et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612042) reports a novel, G-actin–dependent regulation of actin polymerization within spine heads. They show that actin monomer levels are elevated in spines upon activity, with G-actin immobilized by the local enrichment of phosphatidylinositol (3,4,5)-triphosphate (PIP3) within the spine plasma membrane.

scholarly journals The Mechanical Basis of Memory - the MeshCODE Theory

2020 ◽  
Author(s):  
Benjamin T. Goult
Keyword(s):  
Data Storage ◽  
Synaptic Activity ◽  
Physical Location ◽  
Binary Format ◽  
Potential Spike ◽  
Mechanical Basis ◽  
The Mind ◽  
And Storage ◽  
The Brain ◽  
Form Information

One of the major unsolved mysteries of biological science concerns the question of where and in what form information is stored in the brain. I propose that memory is stored in the brain in a mechanically encoded binary format written into the conformations of proteins found in the cell-extracellular matrix adhesions that organise each and every synapse. The MeshCODE framework outlined here represents a unifying theory of data storage in animals, providing read-write storage of both dynamic and persistent information in a binary format. Mechanosensitive proteins that contain force-dependent switches can store information persistently, which can be written or updated using small changes in mechanical force. These mechanosensitive proteins, such as talin, scaffold each synapse, creating a meshwork of switches that together form a code, the so-called MeshCODE. Large signalling complexes assemble on these scaffolds as a function of the switch patterns and these complexes would both stabilise the patterns and coordinate synaptic regulators to dynamically tune synaptic activity. Synaptic transmission and action potential spike trains would operate the cytoskeletal machinery to write and update the synaptic MeshCODEs, thereby propagating this coding throughout the organism. Based on established biophysical principles, such a mechanical basis for memory would provide a physical location for data storage in the brain, with the binary patterns, encoded in the information-storing mechanosensitive molecules in the synaptic scaffolds, and the complexes that form on them, representing the physical location of engrams. Furthermore, the conversion and storage of sensory and temporal inputs into a binary format would constitute an addressable read-write memory system, supporting the view of the mind as an organic supercomputer.

scholarly journals Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis

2009 ◽  
Vol 185 (2) ◽  
pp. 323-339 ◽  
Author(s):  
Pirta Hotulainen ◽  
Olaya Llano ◽  
Sergei Smirnov ◽  
Kimmo Tanhuanpää ◽  
Jan Faix ◽  
...  
Keyword(s):  
Actin Filament ◽  
Dendritic Spines ◽  
Actin Polymerization ◽  
Morphological Changes ◽  
Small Gtpase ◽  
Actin Dynamics ◽  
Excitatory Synapses ◽  
Mature Brain ◽  
Key Steps ◽  
Spine Morphogenesis

Dendritic spines are small protrusions along dendrites where the postsynaptic components of most excitatory synapses reside in the mature brain. Morphological changes in these actin-rich structures are associated with learning and memory formation. Despite the pivotal role of the actin cytoskeleton in spine morphogenesis, little is known about the mechanisms regulating actin filament polymerization and depolymerization in dendritic spines. We show that the filopodia-like precursors of dendritic spines elongate through actin polymerization at both the filopodia tip and root. The small GTPase Rif and its effector mDia2 formin play a central role in regulating actin dynamics during filopodia elongation. Actin filament nucleation through the Arp2/3 complex subsequently promotes spine head expansion, and ADF/cofilin-induced actin filament disassembly is required to maintain proper spine length and morphology. Finally, we show that perturbation of these key steps in actin dynamics results in altered synaptic transmission.

scholarly journals Control of Dendritic Spine Morphological and Functional Plasticity by Small GTPases

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Kevin M. Woolfrey ◽  
Deepak P. Srivastava
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Neuronal Development ◽  
Structural Plasticity ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Abnormal Development ◽  
Actin Dynamics ◽  
Excitatory Synapses ◽  
Spine Structure

Structural plasticity of excitatory synapses is a vital component of neuronal development, synaptic plasticity, and behaviour. Abnormal development or regulation of excitatory synapses has also been strongly implicated in many neurodevelopmental, psychiatric, and neurodegenerative disorders. In the mammalian forebrain, the majority of excitatory synapses are located on dendritic spines, specialized dendritic protrusions that are enriched in actin. Research over recent years has begun to unravel the complexities involved in the regulation of dendritic spine structure. The small GTPase family of proteins have emerged as key regulators of structural plasticity, linking extracellular signals with the modulation of dendritic spines, which potentially underlies their ability to influence cognition. Here we review a number of studies that examine how small GTPases are activated and regulated in neurons and furthermore how they can impact actin dynamics, and thus dendritic spine morphology. Elucidating this signalling process is critical for furthering our understanding of the basic mechanisms by which information is encoded in neural circuits but may also provide insight into novel targets for the development of effective therapies to treat cognitive dysfunction seen in a range of neurological disorders.

scholarly journals The Mechanical Basis of Memory – the MeshCODE Theory

2021 ◽  
Vol 14 ◽  
Author(s):  
Benjamin T. Goult
Keyword(s):  
Data Storage ◽  
Synaptic Activity ◽  
Physical Location ◽  
Binary Format ◽  
Potential Spike ◽  
Mechanical Basis ◽  
The Mind ◽  
And Storage ◽  
The Brain ◽  
Form Information

One of the major unsolved mysteries of biological science concerns the question of where and in what form information is stored in the brain. I propose that memory is stored in the brain in a mechanically encoded binary format written into the conformations of proteins found in the cell-extracellular matrix (ECM) adhesions that organise each and every synapse. The MeshCODE framework outlined here represents a unifying theory of data storage in animals, providing read-write storage of both dynamic and persistent information in a binary format. Mechanosensitive proteins that contain force-dependent switches can store information persistently, which can be written or updated using small changes in mechanical force. These mechanosensitive proteins, such as talin, scaffold each synapse, creating a meshwork of switches that together form a code, the so-called MeshCODE. Large signalling complexes assemble on these scaffolds as a function of the switch patterns and these complexes would both stabilise the patterns and coordinate synaptic regulators to dynamically tune synaptic activity. Synaptic transmission and action potential spike trains would operate the cytoskeletal machinery to write and update the synaptic MeshCODEs, thereby propagating this coding throughout the organism. Based on established biophysical principles, such a mechanical basis for memory would provide a physical location for data storage in the brain, with the binary patterns, encoded in the information-storing mechanosensitive molecules in the synaptic scaffolds, and the complexes that form on them, representing the physical location of engrams. Furthermore, the conversion and storage of sensory and temporal inputs into a binary format would constitute an addressable read-write memory system, supporting the view of the mind as an organic supercomputer.

scholarly journals SULTA4A1 modulates synaptic development and function by promoting the formation of PSD-95/NMDAR complex

2019 ◽  
Author(s):  
Lorenza Culotta ◽  
Benedetta Terragni ◽  
Ersilia Vinci ◽  
Alessandro Sessa ◽  
Vania Broccoli ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Biological Function ◽  
Dendritic Morphology ◽  
Synaptic Activity ◽  
Spine Density ◽  
Neuron Development ◽  
Dendritic Spine Density ◽  
And Function ◽  
The Brain

AbstractSulfotransferase 4A1 (SULT4A1) is a cytosolic sulfotransferase, that is highly conserved across species and extensively expressed in the brain. However, the biological function of SULT4A1 is unclear. SULT4A1 has been implicated in several neuropsychiatric disorders, such as Phelan-McDermid Syndrome and schizophrenia. Here, we investigate the role of SULT4A1 within neuron development and function. Our data demonstrate that SULT4A1 modulates neuronal branching complexity and dendritic spines formation. Moreover, we show that SULT4A1, by negatively regulating the catalytic activity of Pin1 towards PSD-95, facilitates NMDAR synaptic expression and function. Finally, we demonstrate that the pharmacological inhibition of Pin1 reverses the pathological phenotypes of SULT4A1 knockdown neurons by specifically restoring dendritic spine density and rescuing NMDAR-mediated synaptic transmission. Together, these findings identify SULT4A1 as a novel player in neuron development and function by modulating dendritic morphology and synaptic activity.

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