scholarly journals LARGE, an AMPA receptor interactor, plays a large role in long-term memory formation by driving homeostatic scaling-down

2017 ◽  
Author(s):  
Bo Am Seo ◽  
Taesup Cho ◽  
Daniel Z. Lee ◽  
Hwa Young Lee ◽  
Joong-Jae Lee ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Fine Tuning ◽  
Functional Study ◽  
Long Term Memory ◽  
Term Memory ◽  
Scaling Down ◽  
The Brain

AbstractDynamic trafficking of AMPA-type glutamate receptor (AMPA-R) in neuronal cells is a key cellular mechanism for learning and memory in the brain, which is regulated by AMPA-R interacting proteins. LARGE, a protein associated with intellectual disability, was found to be a novel component of the AMPA-R protein complex in our proteomic study. Here, our functional study of LARGE showed that during homeostatic scaling-down, increased LARGE expression at the Golgi apparatus (Golgi) negatively controlled AMPA-R trafficking from the Golgi to the plasma membrane, leading to downregulated surface and synaptic AMPA-R targeting. In LARGE knockdown mice, long-term potentiation (LTP) was occluded by synaptic AMPA-R overloading, resulting in impaired long-term memory formation. These findings indicate that the fine-tuning of AMPA-R trafficking by LARGE at the Golgi is critical for memory stability in the brain. Our study thus provides novel insights into the pathophysiology of brain disorders associated with intellectual disability.

scholarly journals The role of microRNAs in learning and long-term memory

2020 ◽  
Vol 24 (8) ◽  
pp. 885-896
Author(s):  
L. N. Grinkevich
Keyword(s):  
Cognitive Processes ◽  
Regulation Of Gene Expression ◽  
Memory Formation ◽  
Learning Ability ◽  
Long Term Memory ◽  
Term Memory ◽  
Microrna Biogenesis ◽  
The Brain

The mechanisms of long-term memory formation and ways to improve it (in the case of its impairment) remain an extremely difficult problem yet to be solved. Over the recent years, much attention has been paid to microRNAs in this regard. MicroRNAs are unique endogenous non-coding RNAs about 22 nucleotides in length; each can regulate translation of hundreds of messenger RNA targets, thereby controlling entire gene networks. MicroRNAs are widely represented in the central nervous system. A large number of studies are currently being conducted to investigate the role of microRNAs in the brain functioning. A number of microRNAs have been shown to be involved in the process of synaptic plasticity, as well as in the long-term memory formation. Disruption of microRNA biogenesis leads to significant cognitive dysfunctions. Moreover, impaired microRNA biogenesis is one of the causes of the pathogenesis of mental disorders, neurodegenerative illnesses and senile dementia, which are often accompanied by deterioration in the learning ability and by memory impairment. Optimistic predictions are made that microRNAs can be used as targets for therapeutic treatment and for diagnosing the above pathologies. The importance of applications related to microRNAs significantly raises interest in studying their functions in the brain. Thus, this review is focused on the role of microRNAs in cognitive processes. It describes microRNA biogenesis and the role of miRNAs in the regulation of gene expression, as well as the latest achievements in studying the functional role of microRNAs in learning and in long-term memory formation, depending on the activation or inhibition of their expression. The review presents summarized data on the effect of impaired microRNA biogenesis on long-term memory formation, including those associated with sleep deprivation. In addition, analysis is provided of the current literature related to the prospects of improving cognitive processes by influencing microRNA biogenesis via the use of CRISPR/Cas9 technologies and active mental and physical exercises.

scholarly journals Reading Memory Formation from the Eyes

2018 ◽  
Author(s):  
Anne Bergt ◽  
Anne E. Urai ◽  
Tobias H. Donner ◽  
Lars Schwabe
Keyword(s):  
Synaptic Plasticity ◽  
Memory Formation ◽  
Pupil Dilation ◽  
Long Term Memory ◽  
Term Memory ◽  
Pupil Response ◽  
Rapid Formation ◽  
The Brain

At any time, we are processing thousands of stimuli, but only few of them will be remembered hours or days later. Is there any way to predict which ones? Here, we show that the pupil response to ongoing stimuli, an indicator of physiological arousal, is a reliable predictor of long-term memory for these stimuli, over at least one day. Pupil dilation was tracked while participants performed visual and auditory encoding tasks. Memory was tested immediately after encoding and 24 hours later. Irrespective of the encoding modality, trial-by-trial variations in pupil dilation predicted which stimuli were recalled in the immediate and 24 hours-delayed tests. These results show that our eyes may provide a window into the formation of long-term memories. Furthermore, our findings underline the important role of central arousal systems in the rapid formation of memories in the brain, possibly by gating synaptic plasticity mechanisms.

scholarly journals LARGE, an intellectual disability-associated protein, regulates AMPA-type glutamate receptor trafficking and memory

2018 ◽  
Vol 115 (27) ◽  
pp. 7111-7116 ◽  
Author(s):  
Bo Am Seo ◽  
Taesup Cho ◽  
Daniel Z. Lee ◽  
Joong-jae Lee ◽  
Boyoung Lee ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Glutamate Receptor ◽  
Long Term Potentiation ◽  
Fine Tuning ◽  
Functional Study ◽  
Large Gene ◽  
Severe Intellectual Disability ◽  
Glutamate Receptor Trafficking ◽  
Proteomic Study ◽  
The Brain

Mutations in the human LARGE gene result in severe intellectual disability and muscular dystrophy. How LARGE mutation leads to intellectual disability, however, is unclear. In our proteomic study, LARGE was found to be a component of the AMPA-type glutamate receptor (AMPA-R) protein complex, a main player for learning and memory in the brain. Here, our functional study of LARGE showed that LARGE at the Golgi apparatus (Golgi) negatively controlled AMPA-R trafficking from the Golgi to the plasma membrane, leading to down-regulated surface and synaptic AMPA-R targeting. In LARGE knockdown mice, long-term potentiation (LTP) was occluded by synaptic AMPA-R overloading, resulting in impaired contextual fear memory. These findings indicate that the fine-tuning of AMPA-R trafficking by LARGE at the Golgi is critical for hippocampus-dependent memory in the brain. Our study thus provides insights into the pathophysiology underlying cognitive deficits in brain disorders associated with intellectual disability.

scholarly journals Modeling memory consolidation during posttraining periods in cerebellovestibular learning

2015 ◽  
Vol 112 (11) ◽  
pp. 3541-3546 ◽  
Author(s):  
Tadashi Yamazaki ◽  
Soichi Nagao ◽  
William Lennon ◽  
Shigeru Tanaka
Keyword(s):  
Memory Consolidation ◽  
Short Term Memory ◽  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Experimental Results ◽  
Long Term Memory ◽  
Optokinetic Response ◽  
Term Memory

Long-term depression (LTD) at parallel fiber–Purkinje cell (PF–PC) synapses is thought to underlie memory formation in cerebellar motor learning. Recent experimental results, however, suggest that multiple plasticity mechanisms in the cerebellar cortex and cerebellar/vestibular nuclei participate in memory formation. To examine this possibility, we formulated a simple model of the cerebellum with a minimal number of components based on its known anatomy and physiology, implementing both LTD and long-term potentiation (LTP) at PF–PC synapses and mossy fiber–vestibular nuclear neuron (MF–VN) synapses. With this model, we conducted a simulation study of the gain adaptation of optokinetic response (OKR) eye movement. Our model reproduced several important aspects of previously reported experimental results in wild-type and cerebellum-related gene-manipulated mice. First, each 1-h training led to the formation of short-term memory of learned OKR gain at PF–PC synapses, which diminished throughout the day. Second, daily repetition of the training gradually formed long-term memory that was maintained for days at MF–VN synapses. We reproduced such memory formation under various learning conditions. Third, long-term memory formation occurred after training but not during training, indicating that the memory consolidation occurred during posttraining periods. Fourth, spaced training outperformed massed training in long-term memory formation. Finally, we reproduced OKR gain changes consistent with the changes in the vestibuloocular reflex (VOR) previously reported in some gene-manipulated mice.

The Acute Effect of Alcohol on Various Memory Processes

2010 ◽  
Vol 24 (4) ◽  
pp. 249-252 ◽  
Author(s):  
Márk Molnár ◽  
Roland Boha ◽  
Balázs Czigler ◽  
Zsófia Anna Gaál
Keyword(s):  
Low Dose ◽  
Short Term Memory ◽  
Acute Effect ◽  
Long Term Memory ◽  
Term Memory ◽  
Memory Processes ◽  
Different Types ◽  
The Brain ◽  
Legal Consequences

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.

scholarly journals Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice

2021 ◽  
Author(s):  
Kinga K. Borowicz-Reutt ◽  
Monika Banach ◽  
Monika Rudkowska ◽  
Anna Stachniuk
Keyword(s):  
Antiepileptic Drugs ◽  
Second Generation ◽  
Antidepressant Drug ◽  
Experimental Models ◽  
Long Term Memory ◽  
Avoidance Task ◽  
Maximal Electroshock ◽  
Term Memory ◽  
The Brain

Abstract Background Due to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the antielectroshock action of phenytoin and valproate in mice. Materials and methods As a continuation of previous experiments, we examined the effect of sotalol on the action of four chosen second-generation antiepileptic drugs (oxcarbazepine, lamotrigine, pregabalin, and topiramate) against the maximal electroshock in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay, while those of sotalol by liquid chromatography–mass spectrometry. Results Sotalol at doses of up to 100 mg/kg did not affect the electroconvulsive threshold. Applied at doses of 80–100 mg/kg, sotalol did not affect the antielectroshock action of oxcarbazepine, lamotrigine, pregabalin, or topiramate. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory. Finally, sotalol significantly decreased the brain concentrations of lamotrigine and increased those of oxcarbazepine and topiramate. Pharmacokinetic interactions, however, did not influence the final antielectroshock effects of above-mentioned drug combinations. On the other hand, the brain concentrations of sotalol were not changed by second-generation antiepileptics used in this study. Conclusion Sotalol did not reduce the antielectroshock action of four second-generation antiepileptic drugs examined in this study. Therefore, this antidepressant drug should not interfere with antiseizure effects of lamotrigine, oxcarbazepine, pregabalin, and topiramate in patients with epilepsy. To draw final conclusions, our preclinical data should still be confirmed in other experimental models and clinical conditions.

The role of PKMζ in the maintenance of long-term memory: a review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hamish Patel ◽  
Reza Zamani
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Long Term Potentiation ◽  
Global Memory ◽  
Long Term Memory ◽  
Compensatory Mechanism ◽  
Term Memory ◽  
Kinase C

Abstract Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.

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