scholarly journals The novel synaptogenic protein Farp1 links postsynaptic cytoskeletal dynamics and transsynaptic organization

2012 ◽  
Vol 199 (6) ◽  
pp. 985-1001 ◽  
Author(s):  
Lucas Cheadle ◽  
Thomas Biederer
Keyword(s):  
Synapse Formation ◽  
Synaptic Membranes ◽  
Synapse Development ◽  
The Novel ◽  
Spine Density ◽  
Actin Assembly ◽  
Spine Morphology ◽  
Synaptic Complex ◽  
Cytoskeletal Dynamics ◽  
Retrograde Signal

Synaptic adhesion organizes synapses, yet the signaling pathways that drive and integrate synapse development remain incompletely understood. We screened for regulators of these processes by proteomically analyzing synaptic membranes lacking the synaptogenic adhesion molecule SynCAM 1. This identified FERM, Rho/ArhGEF, and Pleckstrin domain protein 1 (Farp1) as strongly reduced in SynCAM 1 knockout mice. Farp1 regulates dendritic filopodial dynamics in immature neurons, indicating roles in synapse formation. Later in development, Farp1 is postsynaptic and its 4.1 protein/ezrin/radixin/moesin (FERM) domain binds SynCAM 1, assembling a synaptic complex. Farp1 increases synapse number and modulates spine morphology, and SynCAM 1 requires Farp1 for promoting spines. In turn, SynCAM 1 loss reduces the ability of Farp1 to elevate spine density. Mechanistically, Farp1 activates the GTPase Rac1 in spines downstream of SynCAM 1 clustering, and promotes F-actin assembly. Farp1 furthermore triggers a retrograde signal regulating active zone composition via SynCAM 1. These results reveal a postsynaptic signaling pathway that engages transsynaptic interactions to coordinate synapse development.

scholarly journals Decreased dendritic spine density and abnormal spine morphology in Fyn knockout mice

2011 ◽  
Vol 1415 ◽  
pp. 96-102 ◽  
Author(s):  
Lenard W. Babus ◽  
Elizabeth M. Little ◽  
Kathleen E. Keenoy ◽  
S. Sakura Minami ◽  
Eric Chen ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Knockout Mice ◽  
Spine Density ◽  
Spine Morphology ◽  
Dendritic Spine Density

scholarly journals Kalirin, a Key Player in Synapse Formation, Is Implicated in Human Diseases

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Prashant Mandela ◽  
Xin-Ming Ma
Keyword(s):  
Learning And Memory ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Pdz Domain ◽  
Long Term Potentiation ◽  
Human Diseases ◽  
Binding Motif ◽  
Spine Density ◽  
Morphological Alterations

Synapse formation is considered to be crucial for learning and memory. Understanding the underlying molecular mechanisms of synapse formation is a key to understanding learning and memory. Kalirin-7, a major isoform of Kalirin in adult rodent brain, is an essential component of mature excitatory synapses. Kalirin-7 interacts with multiple PDZ-domain-containing proteins including PSD95, spinophilin, and GluR1 through its PDZ-binding motif. In cultured hippocampal/cortical neurons, overexpression of Kalirin-7 increases spine density and spine size whereas reduction of endogenous Kalirin-7 expression decreases synapse number, and spine density. In Kalirin-7 knockout mice, spine length, synapse number, and postsynaptic density (PSD) size are decreased in hippocampal CA1 pyramidal neurons; these morphological alterations are accompanied by a deficiency in long-term potentiation (LTP) and a decreased spontaneous excitatory postsynaptic current (sEPSC) frequency. Human Kalirin-7, also known as Duo or Huntingtin-associated protein-interacting protein (HAPIP), is equivalent to rat Kalirin-7. Recent studies show that Kalirin is relevant to many human diseases such as Huntington’s Disease, Alzheimer’s Disease, ischemic stroke, schizophrenia, depression, and cocaine addiction. This paper summarizes our recent understanding of Kalirin function.

scholarly journals Regulation of spine morphology and spine density by NMDA receptor signaling in vivo

2007 ◽  
Vol 104 (49) ◽  
pp. 19553-19558 ◽  
Author(s):  
S. K. Ultanir ◽  
J.-E. Kim ◽  
B. J. Hall ◽  
T. Deerinck ◽  
M. Ellisman ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Signaling ◽  
Spine Density ◽  
Spine Morphology

scholarly journals Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Audrey J. Weber ◽  
Ashley B. Adamson ◽  
Kelsey M. Greathouse ◽  
Julia P. Andrade ◽  
Cameron D. Freeman ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Spine Density ◽  
Control Of Gene Expression ◽  
Spine Morphology ◽  
Dendritic Spine Morphology ◽  
Morphometry Analysis ◽  
Apical Dendrites

AbstractRho-associated kinase isoform 2 (ROCK2) is an attractive drug target for several neurologic disorders. A critical barrier to ROCK2-based research and therapeutics is the lack of a mouse model that enables investigation of ROCK2 with spatial and temporal control of gene expression. To overcome this, we generated ROCK2fl/fl mice. Mice expressing Cre recombinase in forebrain excitatory neurons (CaMKII-Cre) were crossed with ROCK2fl/fl mice (Cre/ROCK2fl/fl), and the contribution of ROCK2 in behavior as well as dendritic spine morphology in the hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) was examined. Cre/ROCK2fl/fl mice spent reduced time in the open arms of the elevated plus maze and increased time in the dark of the light–dark box test compared to littermate controls. These results indicated that Cre/ROCK2fl/fl mice exhibited anxiety-like behaviors. To examine dendritic spine morphology, individual pyramidal neurons in CA1 hippocampus, mPFC, and the BLA were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. In dorsal CA1, Cre/ROCK2fl/fl mice displayed significantly increased thin spine density on basal dendrites and reduced mean spine head volume across all spine types on apical dendrites. In ventral CA1, Cre/ROCK2fl/fl mice exhibited significantly increased spine length on apical dendrites. Spine density and morphology were comparable in the mPFC and BLA between both genotypes. These findings suggest that neuronal ROCK2 mediates spine density and morphology in a compartmentalized manner among CA1 pyramidal cells, and that in the absence of ROCK2 these mechanisms may contribute to anxiety-like behaviors.

scholarly journals Recent advances in branching mechanisms underlying neuronal morphogenesis

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1779 ◽  
Author(s):  
Shalini Menon ◽  
Stephanie Gupton
Keyword(s):  
Intracellular Signaling ◽  
Synapse Formation ◽  
Neuronal Morphogenesis ◽  
Effector Cells ◽  
Signaling Mechanisms ◽  
Recent Advances ◽  
Dendritic Branching ◽  
Branch Formation ◽  
Cytoskeletal Dynamics ◽  
To Receive

Proper neuronal wiring is central to all bodily functions, sensory perception, cognition, memory, and learning. Establishment of a functional neuronal circuit is a highly regulated and dynamic process involving axonal and dendritic branching and navigation toward appropriate targets and connection partners. This intricate circuitry includes axo-dendritic synapse formation, synaptic connections formed with effector cells, and extensive dendritic arborization that function to receive and transmit mechanical and chemical sensory inputs. Such complexity is primarily achieved by extensive axonal and dendritic branch formation and pruning. Fundamental to neuronal branching are cytoskeletal dynamics and plasma membrane expansion, both of which are regulated via numerous extracellular and intracellular signaling mechanisms and molecules. This review focuses on recent advances in understanding the biology of neuronal branching.

Toward a Brain-Inspired Developmental Neural Network Based on Dendritic Spine Dynamics

2021 ◽  
pp. 1-18
Author(s):  
Feifei Zhao ◽  
Yi Zeng ◽  
Jun Bai
Keyword(s):  
Neural Network ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Synapse Formation ◽  
Dynamic Structure ◽  
Classification Performance ◽  
Synaptic Activity ◽  
Data Sets ◽  
Spine Density ◽  
Spine Dynamics

Abstract Neural networks with a large number of parameters are prone to overfitting problems when trained on a relatively small training set. Introducing weight penalties of regularization is a promising technique for solving this problem. Taking inspiration from the dynamic plasticity of dendritic spines, which plays an important role in the maintenance of memory, this letter proposes a brain-inspired developmental neural network based on dendritic spine dynamics (BDNN-dsd). The dynamic structure changes of dendritic spines include appearing, enlarging, shrinking, and disappearing. Such spine plasticity depends on synaptic activity and can be modulated by experiences—in particular, long-lasting synaptic enhancement/suppression (LTP/LTD), coupled with synapse formation (or enlargement)/elimination (or shrinkage), respectively. Subsequently, spine density characterizes an approximate estimate of the total number of synapses between neurons. Motivated by this, we constrain the weight to a tunable bound that can be adaptively modulated based on synaptic activity. Dynamic weight bound could limit the relatively redundant synapses and facilitate the contributing synapses. Extensive experiments demonstrate the effectiveness of our method on classification tasks of different complexity with the MNIST, Fashion MNIST, and CIFAR-10 data sets. Furthermore, compared to dropout and L2 regularization algorithms, our method can improve the network convergence rate and classification performance even for a compact network.

scholarly journals Neurexin-Neuroligin Synaptic Complex Regulates Schizophrenia-Related DISC1/Kal-7/Rac1 “Signalosome”

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Sylwia Owczarek ◽  
Marie Louise Bang ◽  
Vladimir Berezin
Keyword(s):  
Central Nervous System ◽  
Cell Adhesion Molecules ◽  
Synaptic Membranes ◽  
Dependent Manner ◽  
Related Protein ◽  
Synaptic Complex ◽  
The Central Nervous System ◽  
And Function ◽  
Activity Dependent ◽  
The Brain

Neurexins (NXs) and neuroligins (NLs) are cell adhesion molecules that are localized at opposite sites of synaptic membranes. They interact with each other to promote the assembly, maintenance, and function of synapses in the central nervous system. Both NX and NL are cleaved from a membrane-attached intracellular domain in an activity-dependent manner, generating the soluble ectodomain of NX or NL. Expression of theNX1andNX3genes in the brain appears to be regulated by a schizophrenia-related protein, DISC1. Here, we show that soluble ecto-NX1βcan regulate the expression of DISC1 and induce signaling downstream of DISC1. We also show that NL1 binds to a well-characterized DISC1 interaction partner, Kal-7, and this interaction can be compromised by DISC1. Our results indicate that the NX/NL synaptic complex is intrinsically involved in the regulation of DISC1 function, thus contributing to a better understanding of the pathology of schizophrenia.

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