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 Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons

2020 ◽  
Author(s):  
Lauren Tereshko ◽  
Ya Gao ◽  
Brian A. Cary ◽  
Gina G. Turrigiano ◽  
Piali Sengupta
Keyword(s):  
Primary Cilia ◽  
Neuronal Development ◽  
Pyramidal Neurons ◽  
Somatostatin Receptor ◽  
Cognitive Disorders ◽  
Mammalian Brain ◽  
Excitatory Synapses ◽  
Ciliary Signaling ◽  
Neocortical Pyramidal Neurons

ABSTRACTPrimary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured neocortical pyramidal neurons, and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to pyramidal neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses, and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.

scholarly journals p120 Catenin Regulates Dendritic Spine and Synapse Development through Rho-Family GTPases and Cadherins

Neuron ◽  
2006 ◽  
Vol 51 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Lisa P. Elia ◽  
Miya Yamamoto ◽  
Keling Zang ◽  
Louis F. Reichardt
Keyword(s):  
Dendritic Spine ◽  
Synapse Development ◽  
P120 Catenin ◽  
Rho Family Gtpases ◽  
Rho Family

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.

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 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 Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Lauren Tereshko ◽  
Ya Gao ◽  
Brian A Cary ◽  
Gina G Turrigiano ◽  
Piali Sengupta
Keyword(s):  
Primary Cilia ◽  
Neuronal Development ◽  
Pyramidal Neurons ◽  
Somatostatin Receptor ◽  
Cognitive Disorders ◽  
Mammalian Brain ◽  
Excitatory Synapses ◽  
Ciliary Signaling ◽  
Neocortical Pyramidal Neurons

Primary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured rat neocortical pyramidal neurons and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to excitatory neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.

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 Proteasome-mediated Degradation of Rac1-GTP during Epithelial Cell Scattering

2006 ◽  
Vol 17 (5) ◽  
pp. 2236-2242 ◽  
Author(s):  
Emma A. Lynch ◽  
Jennifer Stall ◽  
Gudila Schmidt ◽  
Philippe Chavrier ◽  
Crislyn D'Souza-Schorey
Keyword(s):  
Epithelial Cell ◽  
Actin Polymerization ◽  
Actin Dynamics ◽  
Cell Contacts ◽  
Rho Family Gtpases ◽  
Cell Scattering ◽  
Rho Family ◽  
Powerful Mechanism ◽  
Sustained Activation ◽  
Cell Cell

Epithelial cells disassemble their adherens junctions and “scatter” during processes such as tumor cell invasion as well as some stages of embryonic development. Control of actin polymerization is a powerful mechanism for regulating the strength of cell–cell adhesion. In this regard, studies have shown that sustained activation of Rac1, a well-known regulator of actin dynamics, results in the accumulation of polymerized actin at cell–cell contacts in epithelia and an increase in E-cadherin–mediated adhesion. Here we show that active Rac1 is ubiquitinated and subject to proteasome-mediated degradation during the early stages of epithelial cell scattering. These findings delineate a mechanism for the down-regulation of Rac1 in the disassembly of epithelial cell–cell contacts and support the emerging theme that UPS-mediated degradation of the Rho family GTPases may serve as an efficient mechanism for GTPase deactivation in the sustained presence of Dbl-exchange factors.

Synaptic organization of the gustatory NST

1994 ◽  
Vol 52 ◽  
pp. 150-151
Author(s):  
M. C. Whitehead
Keyword(s):  
Central Nervous System ◽  
Dendritic Spines ◽  
Fundamental Problem ◽  
Cell Types ◽  
Brain Regions ◽  
Excitatory Synapses ◽  
Solitary Tract ◽  
Synaptic Organization ◽  
Synaptic Junctions ◽  
Afferent Terminals

A fundamental problem in taste research is to determine how gustatory signals are processed and disseminated in the mammalian central nervous system. An important first step toward understanding information processing is the identification of cell types in the nucleus of the solitary tract (NST) and their synaptic relationships with oral primary afferent terminals. Facial and glossopharyngeal (LIX) terminals in the hamster were labelled with HRP, examined with EM, and characterized as containing moderate concentrations of medium-sized round vesicles, and engaging in asymmetrical synaptic junctions. Ultrastructurally the endings resemble excitatory synapses in other brain regions.Labelled facial afferent endings in the RC subdivision synapse almost exclusively with distal dendrites and dendritic spines of NST cells. Most synaptic relationships between the facial synapses and the dendrites are simple. However, 40% of facial endings engage in complex synaptic relationships within glomeruli containing unlabelled axon endings particularly ones termed "SP" endings. SP endings are densely packed with small, pleomorphic vesicles and synapse with both the facial endings and their postsynaptic dendrites by means of nearly symmetrical junctions.

Three-dimensional structure of dendritic spines, neuronal specializations that impart both stability and flexibility to synaptic function

1993 ◽  
Vol 51 ◽  
pp. 92-93
Author(s):  
Kristen M. Harris
Keyword(s):  
Dendritic Spines ◽  
Three Dimensional ◽  
Synaptic Function ◽  
Dimensional Structure ◽  
Excitatory Synapses ◽  
Concept Of Function ◽  
Section Electron ◽  
High Quality Information ◽  
The Central Nervous System ◽  
Mathematical Analyses

Dendritic spines are the tiny protrusions that stud the surface of many neurons and they are the location of over 90% of all excitatory synapses that occur in the central nervous system. Their small size and variable shapes has in large part made detailed study of their structure refractory to conventional light microscopy and single section electron microscopy (EM). Yet their widespread occurrence and likely involvement in learning and memory has motivated extensive efforts to obtain quantitative descriptions of spines in both steady state and dynamic conditions. Since the seminal mathematical analyses of D’Arcy Thompson, the power of establishing quantitatively key parameters of structure has become recognized as a foundation of successful biological inquiry. For dendritic spines highly precise determinations of structure and its variation are proving themselves as the kingpin for establishing a valid concept of function. The recent conjunction of high quality information about the structure, function, and theoretical implications of dendritic spines has produced a flurry of new considerations of their role in synaptic transmission.

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