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 Synapses and Dendritic Spines as Pathogenic Targets in Alzheimer’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Wendou Yu ◽  
Bingwei Lu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Molecular Mechanisms ◽  
Excitatory Synapses ◽  
Dendritic Shaft ◽  
Spine Pathology ◽  
Dynamic Structures

Synapses are sites of cell-cell contacts that transmit electrical or chemical signals in the brain. Dendritic spines are protrusions on dendritic shaft where excitatory synapses are located. Synapses and dendritic spines are dynamic structures whose plasticity is thought to underlie learning and memory. No wonder neurobiologists are intensively studying mechanisms governing the structural and functional plasticity of synapses and dendritic spines in an effort to understand and eventually treat neurological disorders manifesting learning and memory deficits. One of the best-studied brain disorders that prominently feature synaptic and dendritic spine pathology is Alzheimer’s disease (AD). Recent studies have revealed molecular mechanisms underlying the synapse and spine pathology in AD, including a role for mislocalized tau in the postsynaptic compartment. Synaptic and dendritic spine pathology is also observed in other neurodegenerative disease. It is possible that some common pathogenic mechanisms may underlie the synaptic and dendritic spine pathology in neurodegenerative diseases.

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.

Dendritic Spine Remodeling After Spinal Cord Injury Alters Neuronal Signal Processing

2009 ◽  
Vol 102 (4) ◽  
pp. 2396-2409 ◽  
Author(s):  
Andrew M. Tan ◽  
Jin-Sung Choi ◽  
Stephen G. Waxman ◽  
Bryan C. Hains
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Synaptic Transmission ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Nociceptive Neurons ◽  
Spine Shape ◽  
Cord Injury ◽  
Dendritic Spine Morphology ◽  
Neuronal Signal

Central sensitization, a prolonged hyperexcitability of dorsal horn nociceptive neurons, is a major contributor to abnormal pain processing after spinal cord injury (SCI). Dendritic spines are micron-sized dendrite protrusions that can regulate the efficacy of synaptic transmission. Here we used a computational approach to study whether changes in dendritic spine shape, density, and distribution can individually, or in combination, adversely modify the input–output function of a postsynaptic neuron to create a hyperexcitable neuronal state. The results demonstrate that a conversion from thin-shaped to more mature, mushroom-shaped spine structures results in enhanced synaptic transmission and fidelity, improved frequency-following ability, and reduced inhibitory gating effectiveness. Increasing the density and redistributing spines toward the soma results in a greater probability of action potential activation. Our results demonstrate that changes in dendritic spine morphology, documented in previous studies on spinal cord injury, contribute to the generation of pain following SCI.

scholarly journals BDNF signaling during the lifetime of dendritic spines

2020 ◽  
Vol 382 (1) ◽  
pp. 185-199 ◽  
Author(s):  
Marta Zagrebelsky ◽  
Charlotte Tacke ◽  
Martin Korte
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Neurological Disorders ◽  
Current Knowledge ◽  
Conclusive Evidence ◽  
Excitatory Synapses ◽  
Neuronal Homeostasis ◽  
Bdnf Signaling ◽  
Spine Number

Abstract Dendritic spines are tiny membrane specialization forming the postsynaptic part of most excitatory synapses. They have been suggested to play a crucial role in regulating synaptic transmission during development and in adult learning processes. Changes in their number, size, and shape are correlated with processes of structural synaptic plasticity and learning and memory and also with neurodegenerative diseases, when spines are lost. Thus, their alterations can correlate with neuronal homeostasis, but also with dysfunction in several neurological disorders characterized by cognitive impairment. Therefore, it is important to understand how different stages in the life of a dendritic spine, including formation, maturation, and plasticity, are strictly regulated. In this context, brain-derived neurotrophic factor (BDNF), belonging to the NGF-neurotrophin family, is among the most intensively investigated molecule. This review would like to report the current knowledge regarding the role of BDNF in regulating dendritic spine number, structure, and plasticity concentrating especially on its signaling via its two often functionally antagonistic receptors, TrkB and p75NTR. In addition, we point out a series of open points in which, while the role of BDNF signaling is extremely likely conclusive, evidence is still missing.

scholarly journals Dendritic spine geometry can localize GTPase signaling in neurons

2015 ◽  
Vol 26 (22) ◽  
pp. 4171-4181 ◽  
Author(s):  
Samuel A. Ramirez ◽  
Sridhar Raghavachari ◽  
Daniel J. Lew
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Primary Cilia ◽  
Reaction Diffusion ◽  
Reaction Diffusion Equations ◽  
Mammalian Brain ◽  
Excitatory Synapses ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
Sustained Activation

Dendritic spines are the postsynaptic terminals of most excitatory synapses in the mammalian brain. Learning and memory are associated with long-lasting structural remodeling of dendritic spines through an actin-mediated process regulated by the Rho-family GTPases RhoA, Rac, and Cdc42. These GTPases undergo sustained activation after synaptic stimulation, but whereas Rho activity can spread from the stimulated spine, Cdc42 activity remains localized to the stimulated spine. Because Cdc42 itself diffuses rapidly in and out of the spine, the basis for the retention of Cdc42 activity in the stimulated spine long after synaptic stimulation has ceased is unclear. Here we model the spread of Cdc42 activation at dendritic spines by means of reaction-diffusion equations solved on spine-like geometries. Excitable behavior arising from positive feedback in Cdc42 activation leads to spreading waves of Cdc42 activity. However, because of the very narrow neck of the dendritic spine, wave propagation is halted through a phenomenon we term geometrical wave-pinning. We show that this can account for the localization of Cdc42 activity in the stimulated spine, and, of interest, retention is enhanced by high diffusivity of Cdc42. Our findings are broadly applicable to other instances of signaling in extreme geometries, including filopodia and primary cilia.

scholarly journals Astrocytic control of synaptic function

2017 ◽  
Vol 372 (1715) ◽  
pp. 20160154 ◽  
Author(s):  
Thomas Papouin ◽  
Jaclyn Dunphy ◽  
Michaela Tolman ◽  
Jeannine C. Foley ◽  
Philip G. Haydon
Keyword(s):  
Information Processing ◽  
Synaptic Transmission ◽  
Intracellular Calcium ◽  
Synaptic Function ◽  
Homeostatic Plasticity ◽  
Complex Dynamic ◽  
Signalling Molecules ◽  
The Past ◽  
Global Fluctuations ◽  
The Brain

Astrocytes intimately interact with synapses, both morphologically and, as evidenced in the past 20 years, at the functional level. Ultrathin astrocytic processes contact and sometimes enwrap the synaptic elements, sense synaptic transmission and shape or alter the synaptic signal by releasing signalling molecules. Yet, the consequences of such interactions in terms of information processing in the brain remain very elusive. This is largely due to two major constraints: (i) the exquisitely complex, dynamic and ultrathin nature of distal astrocytic processes that renders their investigation highly challenging and (ii) our lack of understanding of how information is encoded by local and global fluctuations of intracellular calcium concentrations in astrocytes. Here, we will review the existing anatomical and functional evidence of local interactions between astrocytes and synapses, and how it underlies a role for astrocytes in the computation of synaptic information. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

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.

Fhod3 Controls the Dendritic Spine Morphology of Specific Subpopulations of Pyramidal Neurons in the Mouse Cerebral Cortex

2020 ◽  
Author(s):  
Hikmawan Wahyu Sulistomo ◽  
Takayuki Nemoto ◽  
Yohko Kage ◽  
Hajime Fujii ◽  
Taku Uchida ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Cell Type ◽  
Spine Morphology ◽  
Mouse Cerebral Cortex ◽  
Specific Manner ◽  
Cell Type Specific ◽  
The Brain ◽  
Spine Morphogenesis

Abstract Changes in the shape and size of the dendritic spines are critical for synaptic transmission. These morphological changes depend on dynamic assembly of the actin cytoskeleton and occur differently in various types of neurons. However, how the actin dynamics are regulated in a neuronal cell type-specific manner remains largely unknown. We show that Fhod3, a member of the formin family proteins that mediate F-actin assembly, controls the dendritic spine morphogenesis of specific subpopulations of cerebrocortical pyramidal neurons. Fhod3 is expressed specifically in excitatory pyramidal neurons within layers II/III and V of restricted areas of the mouse cerebral cortex. Immunohistochemical and biochemical analyses revealed the accumulation of Fhod3 in postsynaptic spines. Although targeted deletion of Fhod3 in the brain did not lead to any defects in the gross or histological appearance of the brain, the dendritic spines in pyramidal neurons within presumptive Fhod3-positive areas were morphologically abnormal. In primary cultures prepared from the Fhod3-depleted cortex, defects in spine morphology were only detected in Fhod3 promoter-active cells, a small population of pyramidal neurons, and not in Fhod3 promoter-negative pyramidal neurons. Thus, Fhod3 plays a crucial role in dendritic spine morphogenesis only in a specific population of pyramidal neurons in a cell type-specific manner.

scholarly journals Dendritic Spine Initiation in Brain Development, Learning and Diseases and Impact of BAR-Domain Proteins

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2392 ◽  
Author(s):  
Pushpa Khanal ◽  
Pirta Hotulainen
Keyword(s):  
Brain Development ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Spine Density ◽  
Bar Domain ◽  
Neuronal Dendrites ◽  
Bar Domain Proteins ◽  
Before And After

Dendritic spines are small, bulbous protrusions along neuronal dendrites where most of the excitatory synapses are located. Dendritic spine density in normal human brain increases rapidly before and after birth achieving the highest density around 2–8 years. Density decreases during adolescence, reaching a stable level in adulthood. The changes in dendritic spines are considered structural correlates for synaptic plasticity as well as the basis of experience-dependent remodeling of neuronal circuits. Alterations in spine density correspond to aberrant brain function observed in various neurodevelopmental and neuropsychiatric disorders. Dendritic spine initiation affects spine density. In this review, we discuss the importance of spine initiation in brain development, learning, and potential complications resulting from altered spine initiation in neurological diseases. Current literature shows that two Bin Amphiphysin Rvs (BAR) domain-containing proteins, MIM/Mtss1 and SrGAP3, are involved in spine initiation. We review existing literature and open databases to discuss whether other BAR-domain proteins could also take part in spine initiation. Finally, we discuss the potential molecular mechanisms on how BAR-domain proteins could regulate spine initiation.

scholarly journals Regulation of dendritic spine growth through activity-dependent recruitment of the brain-enriched Na+/H+ exchanger NHE5

2011 ◽  
Vol 22 (13) ◽  
pp. 2246-2257 ◽  
Author(s):  
Graham H. Diering ◽  
Fergil Mills ◽  
Shernaz X. Bamji ◽  
Masayuki Numata
Keyword(s):  
Nmda Receptor ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Molecular Mechanisms ◽  
Fluorescent Protein ◽  
Receptor Activation ◽  
Neuronal Activation ◽  
Activity Dependent ◽  
The Brain ◽  
Nmda Receptor Activation

Subtle changes in cellular and extracellular pH within the physiological range have profound impacts on synaptic activities. However, the molecular mechanisms underlying local pH regulation at synapses and their influence on synaptic structures have not been elucidated. Dendritic spines undergo dynamic structural changes in response to neuronal activation, which contributes to induction and long-term maintenance of synaptic plasticity. Although previous studies have indicated the importance of cytoskeletal rearrangement, vesicular trafficking, cell signaling, and adhesion in this process, much less is known about the involvement of ion transporters. In this study we demonstrate that N-methyl-d-aspartate (NMDA) receptor activation causes recruitment of the brain-enriched Na+/H+ exchanger NHE5 from endosomes to the plasma membrane. Concomitantly, real-time imaging of green fluorescent protein–tagged NHE5 revealed that NMDA receptor activation triggers redistribution of NHE5 to the spine head. We further show that neuronal activation causes alkalinization of dendritic spines following the initial acidification, and suppression of NHE5 significantly retards the activity-induced alkalinization. Perturbation of NHE5 function induces spontaneous spine growth, which is reversed by inhibition of NMDA receptors. In contrast, overexpression of NHE5 inhibits spine growth in response to neuronal activity. We propose that NHE5 constrains activity-dependent dendritic spine growth via a novel, pH-based negative-feedback mechanism.

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