Long-term Memory Upscales Volume of Postsynaptic Densities in the Process that Requires Autophosphorylation of αCaMKII

2019 ◽  
Vol 30 (4) ◽  
pp. 2573-2585 ◽  
Author(s):  
Małgorzata Alicja Śliwińska ◽  
Anna Cały ◽  
Malgorzata Borczyk ◽  
Magdalena Ziółkowska ◽  
Edyta Skonieczna ◽  
...  

Abstract It is generally accepted that formation and storage of memory relies on alterations of the structure and function of brain circuits. However, the structural data, which show learning-induced and long-lasting remodeling of synapses, are still very sparse. Here, we reconstruct 1927 dendritic spines and their postsynaptic densities (PSDs), representing a postsynaptic part of the glutamatergic synapse, in the hippocampal area CA1 of the mice that underwent spatial training. We observe that in young adult (5 months), mice volume of PSDs, but not the volume of the spines, is increased 26 h after the training. The training-induced growth of PSDs is specific for the dendritic spines that lack smooth endoplasmic reticulum and spine apparatuses, and requires autophosphorylation of αCaMKII. Interestingly, aging alters training-induced ultrastructural remodeling of dendritic spines. In old mice, both the median volumes of dendritic spines and PSDs shift after training toward bigger values. Overall, our data support the hypothesis that formation of memory leaves long-lasting footprint on the ultrastructure of brain circuits; however, the form of circuit remodeling changes with age.

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Yelena D Kulik ◽  
Deborah J Watson ◽  
Guan Cao ◽  
Masaaki Kuwajima ◽  
Kristen M Harris

Long-term potentiation (LTP), an increase in synaptic efficacy following high-frequency stimulation, is widely considered a mechanism of learning. LTP involves local remodeling of dendritic spines and synapses. Smooth endoplasmic reticulum (SER) and endosomal compartments could provide local stores of membrane and proteins, bypassing the distant Golgi apparatus. To test this hypothesis, effects of LTP were compared to control stimulation in rat hippocampal area CA1 at postnatal day 15 (P15). By two hours, small spines lacking SER increased after LTP, whereas large spines did not change in frequency, size, or SER content. Total SER volume decreased after LTP consistent with transfer of membrane to the added spines. Shaft SER remained more abundant in spiny than aspiny dendritic regions, apparently supporting the added spines. Recycling endosomes were elevated specifically in small spines after LTP. These findings suggest local secretory trafficking contributes to LTP-induced synaptogenesis and primes the new spines for future plasticity.


Author(s):  
Lia Almeida Mapurunga ◽  
Elcyana Bezerra Elcyana Bezerra Carvalho

A neurociência é uma ciência natural que estuda a função e a estrutura, que compõem o cérebro. A educação, embora tenha outra natureza, tem tido muitos benefícios com as contribuições que a neurociência tem para oferecer. Como o cérebro aprende e por que aprende traz para o ensino o objetivo e a função de criar condições (entre estratégias, recursos e adequação do meio), para que ocorra a aprendizagem. E, para que essa ocorra, é necessário que as funções mentais superiores, como a memória, estejam envolvidas. O objetivo deste estudo consiste em fazer uma revisão de literatura para conhecer a função da memória de longo prazo na aprendizagem, analisar os mecanismos neurobiológicos, que ocorrem durante esse processo e algumas estratégias de aprendizagem, que se utilizam da memória como recurso. Para isso, foi realizado no período de agosto a outubro de 2016, um levantamento bibliográfico nas bases de dados Scielo, Capes, Bireme e Google Acadêmico, buscando artigos científicos, que poderiam trazer alguma contribuição na construção dessa pesquisa. Foram selecionados, preferencialmente, os que continham enfoque na relação entre aprendizagem e memória, tanto na perspectiva da neurociência, quanto da psicologia cognitiva, trazendo argumentos que pudessem  comprovar o entendimento das estratégias de aprendizagem, a partir da memória de longo prazo. Também foram selecionados livros que apresentavam apoio às temáticas discorridas para esse trabalho, possibilitando essa relação. Os resultados apontam que estratégias de aprendizagens, que utilizam a memória, produzem efeitos positivos para a retenção de longo prazo.Palavras-chave: Aprendizagem. Neurociências. Estratégias de Aprendizagem.AbstractNeuroscience is a natural science that studies the function and structure that forms the brain. Although education has another nature, it has had many benefits from the contributions that neuroscience has to offer. How the brain learns and why it learns brings to teaching the intent and function to create conditions (among strategies, resources and suitability to the environment) so that learning can happen. And, for it to occur, it is  necessary that higher mental functions, such as memory, beinvolved. The purpose of this study is to do a literature review to get to know the function of long-term memory on the learning process, to analyze the neurobiological mechanisms that happen during that process, and some learning strategies that use memory as a resource. Therefore a bibliographical survey was conducted at the databases Scielo, Capes, Bireme and Academic Google, from August to October 2016, searching for scientific articles that could contribute somehow on the construction of this research. The articles that used the neuroscience perspective or the cognitive psychology to focus on the relationship  between learning and memory were chosen, preferentially those whose arguments could prove the  learning strategies understanding about he long-term memory. Books supporting the themes discussed for this work were also selected, creating, therefore, a relationship. The results show that learning strategies that use memory have positive effects for long-term retention.Keywords: Learning. Neuroscience. Learning Strategies.


2020 ◽  
Author(s):  
Yanrui Yang ◽  
Jiang Chen ◽  
Xue Chen ◽  
Di Li ◽  
Jianfeng He ◽  
...  

AbstractDendritic spines of excitatory neurons undergo activity-dependent structural and functional plasticity, which are cellular correlates of learning and memory. However, mechanisms underlying the rapid morphological changes immediately after NMDAR-mediated Ca2+ influx into spines remain poorly understood. Here we report that endophilin A1, a neuronal N-BAR protein, orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in the induction phase of long-term potentiation (LTP). Upon LTP induction, Ca2+/calmodulin enhances its binding to both membrane and p140Cap, a cytoskeleton regulator. As a result, endophilin A1 rapidly associates with the relaxed plasma membrane and promotes actin polymerization, leading to acute expansion of spine head. Moreover, not only the p140Cap-binding, but also calmodulin- and membrane-binding capacities of endophilin A1 are required for LTP and long-term memory. Thus, endophilin A1 functions as calmodulin effector to drive spine enlargement in response to Ca2+ influx in the initial phase of structural plasticity.


2021 ◽  
Vol 220 (6) ◽  
Author(s):  
Yanrui Yang ◽  
Jiang Chen ◽  
Xue Chen ◽  
Di Li ◽  
Jianfeng He ◽  
...  

Induction of long-term potentiation (LTP) in excitatory neurons triggers a large transient increase in the volume of dendritic spines followed by decays to sustained size expansion, a process termed structural LTP (sLTP) that contributes to the cellular basis of learning and memory. Although mechanisms regulating the early and sustained phases of sLTP have been studied intensively, how the acute spine enlargement immediately after LTP stimulation is achieved remains elusive. Here, we report that endophilin A1 orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in NMDAR-mediated LTP. Upon LTP induction, Ca2+/calmodulin enhances binding of endophilin A1 to both membrane and p140Cap, a cytoskeletal regulator. Consequently, endophilin A1 rapidly localizes to the plasma membrane and recruits p140Cap to promote local actin polymerization, leading to spine head expansion. Moreover, its molecular functions in activity-induced rapid spine growth are required for LTP and long-term memory. Thus, endophilin A1 serves as a calmodulin effector to drive acute structural plasticity necessary for learning and memory.


2020 ◽  
Vol 117 (36) ◽  
pp. 22128-22134
Author(s):  
Xinyu Gu ◽  
Nicholas P. Schafer ◽  
Qian Wang ◽  
Sarah S. Song ◽  
Mingchen Chen ◽  
...  

Dendritic spines are tiny membranous protrusions on the dendrites of neurons. Dendritic spines change shape in response to input signals, thereby strengthening the connections between neurons. The growth and stabilization of dendritic spines is thought to be essential for maintaining long-term memory. Actin cytoskeleton remodeling in spines is a key element of their formation and growth. More speculatively, the aggregation of CPEB3, a functional prion that binds RNA, has been reported to be involved in the maintenance of long-term memory. Here we study the interaction between actin and CPEB3 and propose a molecular model for the complex structure of CPEB3 and an actin filament (F-actin). The results of our computational modeling, including both energetic and structural analyses, are compared with novel data from peptide array experiments. Our model of the CPEB3/F-actin interaction suggests that F-actin potentially triggers the aggregation-prone structural transition of a short CPEB3 sequence by zipping it into a beta-hairpin form. We also propose that the CPEB3/F-actin interaction might be regulated by the SUMOylation of CPEB3, based on bioinformatic searches for potential SUMOylation sites as well as SUMO interacting motifs in CPEB3. On the basis of these results and the existing literature, we put forward a possible molecular mechanism underlying long-term memory that involves CPEB3’s binding to actin, its aggregation, and its regulation by SUMOylation.


2021 ◽  
Vol 14 (7) ◽  
pp. 607
Author(s):  
Irina S. Sadovnikova ◽  
Artem P. Gureev ◽  
Daria A. Ignatyeva ◽  
Maria V. Gryaznova ◽  
Ekaterina V. Chernyshova ◽  
...  

Aging is one of the most serious factors for central nervous dysfunctions, which lead to cognitive impairment. New highly effective drugs are required to slow the development of cognitive dysfunction. This research studied the effect of dimethyl fumarate (DMF), methylene blue (MB), and resveratrol (RSV) on the cognitive functions of 15-month-old mice and their relationship to the maintenance of mitochondrial quality control in the brain and the bacterial composition of the gut microbiome. We have shown that studied compounds enhance mitochondrial biogenesis, mitophagy, and antioxidant defense in the hippocampus of 15-month-old mice via Nrf2/ARE pathway activation, which reduces the degree of oxidative damage to mtDNA. It is manifested in the improvement of short-term and long-term memory. We have also shown that memory improvement correlates with levels of Roseburia, Oscillibacter, Christensenellaceae R-7, Negativibacillus, and Faecalibaculum genera of bacteria. At the same time, long-term treatment by MB induced a decrease in gut microbiome diversity, but the other markers of dysbiosis were not observed. Thus, Nrf2/ARE activators have an impact on mitochondrial quality control and are associated with a positive change in the composition of the gut microbiome, which together lead to an improvement in memory in aged mice.


1990 ◽  
Vol 45 (3) ◽  
pp. B101-B104 ◽  
Author(s):  
J. F. Flood ◽  
J. E. Morley

Sign in / Sign up

Export Citation Format

Share Document