706. Wnt/β-Catenin Pathway Contributions to Dendritic Spine and Glutamatergic Synapse Formation Responsive to Lithium-Mediated GSK3 Inhibition

2017 ◽  
Vol 81 (10) ◽  
pp. S286
Author(s):  
Robert Stanley ◽  
Pierre-Marie Martin ◽  
Adam Ross ◽  
Andiara Freitas ◽  
Jillian Iafrati ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Synapse Formation ◽  
Glutamatergic Synapse

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 An APPL1/Akt signaling complex regulates dendritic spine and synapse formation in hippocampal neurons

2011 ◽  
Vol 46 (3) ◽  
pp. 633-644 ◽  
Author(s):  
Devi Majumdar ◽  
Caroline A. Nebhan ◽  
Lan Hu ◽  
Bridget Anderson ◽  
Donna J. Webb
Keyword(s):  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Synapse Formation ◽  
Akt Signaling ◽  
Signaling Complex

Actin capping protein in dendritic spine development and synapse formation

2011 ◽  
Vol 71 ◽  
pp. e60
Author(s):  
Yanjie Fan ◽  
Xin Tang ◽  
Eric Vitriol ◽  
Gong Chen ◽  
James Zheng
Keyword(s):  
Dendritic Spine ◽  
Synapse Formation ◽  
Capping Protein ◽  
Spine Development ◽  
Actin Capping Protein ◽  
Actin Capping

scholarly journals Depolarizing GABA Transmission Restrains Activity-Dependent Glutamatergic Synapse Formation in the Developing Hippocampal Circuit

2019 ◽  
Author(s):  
Christopher K. Salmon ◽  
Horia Pribiag ◽  
W. Todd Farmer ◽  
Scott Cameron ◽  
Emma V. Jones ◽  
...  
Keyword(s):  
Neural Activity ◽  
Pyramidal Neurons ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Reversal Potential ◽  
Glutamatergic Synapse ◽  
Inhibitory Neurotransmitter ◽  
Key Factor ◽  
Circuit Development ◽  
Activity Dependent

ABSTRACTGABA is the main inhibitory neurotransmitter in the mature brain but has the paradoxical property of depolarizing neurons during early development. Depolarization provided by GABAA transmission during this early phase regulates neural stem cell proliferation, neural migration, neurite outgrowth, synapse formation, and circuit refinement, making GABA a key factor in neural circuit development. Importantly, depending on the context, depolarizing GABAA transmission can either drive neural activity, or inhibit it through shunting inhibition. The varying roles of depolarizing GABAA transmission during development, and its ability to both drive and inhibit neural activity, makes it a difficult developmental cue to study. This is particularly true in the later stages of development, when the majority of synapses form and GABAA transmission switches from depolarizing to hyperpolarizing. Here we addressed the importance of depolarizing but inhibitory (or shunting) GABAA transmission in glutamatergic synapse formation in hippocampal CA1 pyramidal neurons. We first showed that the developmental depolarizing-to-hyperpolarizing switch in GABAA transmission is recapitulated in organotypic hippocampal slice cultures. Based on the expression profile of K+-Cl- co-transporter 2 (KCC2) and changes in the GABA reversal potential, we pinpointed the timing of the switch from depolarizing to hyperpolarizing GABAA transmission in CA1 neurons. We found that blocking depolarizing but shunting GABAA transmission increased excitatory synapse number and strength, indicating that depolarizing GABAA transmission can restrain glutamatergic synapse formation. The increase in glutamatergic synapses was activity-dependent, but independent of BDNF signalling. Importantly, the elevated number of synapses was stable for more than a week after GABAA inhibitors were washed out. Together these findings point to the ability of immature GABAergic transmission to restrain glutamatergic synapse formation and suggest an unexpected role for depolarizing GABAA transmission in shaping excitatory connectivity during neural circuit development.

scholarly journals Protecting synapses from amyloid β-associated degeneration by manipulations of Wnt/planar cell polarity signaling

2020 ◽  
Author(s):  
Bo Feng ◽  
Andiara E. Freitas ◽  
Runyi Tian ◽  
Yeo Rang Lee ◽  
Akumbir S. Grewal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Planar Cell Polarity ◽  
Synapse Formation ◽  
Amyloid Β ◽  
Glutamatergic Synapse ◽  
Aβ Oligomers ◽  
Synapse Loss ◽  
Synapse Maintenance ◽  
Pcp Signaling

ABSTRACTSynapse loss is an early event in Alzheimer’s disease and is thought to be associated with amyloid pathology and caused by Amyloid β (Aβ) oligomers. Whether and how Aβ oligomers directly target signaling pathways for glutamatergic synapse maintenance is unknown. Glutamatergic synapse development is controlled by the opposing functions of Celsr3 and Vangl2, core components of the Wnt/planar cell polarity (PCP) signaling pathway, functioning directly in the synapses. Celsr3 promotes synapse formation, whereas Vangl2 inhibits synapse formation. Here we show that oligomeric Aβ binds to Celsr3 and assists Vangl2 in disassembling synapses by disrupting the intercellular Celsr3/Frizzled3-Celsr3 complex, essential for PCP signaling. Together with Vangl2, a Wnt receptor, Ryk, is also required for Aβ oligomer-induced synapse loss in a mouse model of Alzheimer’s disease, 5XFAD, where conditional Ryk knockout protected synapses and preserved cognitive function. Our study reveals a fine balance of Wnt/PCP signaling components in glutamatergic synapse maintenance and suggests that overproduced Aβ oligomers may lead to excessive synapse loss by tipping this balance. Together with previous reports that an inhibitor of Wnt/Ryk signaling, WIF1, is found reduced in Alzheimer’s disease patients, our results suggest that the imbalance of PCP signaling in these patients may contribute to synapse loss in Alzheimer’s disease and manipulating Wnt/PCP signaling may preserve synapses and cognitive function.

scholarly journals ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity

2015 ◽  
Vol 210 (2) ◽  
pp. 225-242 ◽  
Author(s):  
Karen A. Newell-Litwa ◽  
Mathilde Badoual ◽  
Hannelore Asmussen ◽  
Heather Patel ◽  
Leanna Whitmore ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Actin Polymerization ◽  
Synapse Formation ◽  
Leading Edge ◽  
Actin Remodeling ◽  
Rac1 Activity ◽  
Dendritic Spine Morphology ◽  
Filament Bundles ◽  
Migratory Cells

RhoGTPases organize the actin cytoskeleton to generate diverse polarities, from front–back polarity in migrating cells to dendritic spine morphology in neurons. For example, RhoA through its effector kinase, RhoA kinase (ROCK), activates myosin II to form actomyosin filament bundles and large adhesions that locally inhibit and thereby polarize Rac1-driven actin polymerization to the protrusions of migratory fibroblasts and the head of dendritic spines. We have found that the two ROCK isoforms, ROCK1 and ROCK2, differentially regulate distinct molecular pathways downstream of RhoA, and their coordinated activities drive polarity in both cell migration and synapse formation. In particular, ROCK1 forms the stable actomyosin filament bundles that initiate front–back and dendritic spine polarity. In contrast, ROCK2 regulates contractile force and Rac1 activity at the leading edge of migratory cells and the spine head of neurons; it also specifically regulates cofilin-mediated actin remodeling that underlies the maturation of adhesions and the postsynaptic density of dendritic spines.

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