scholarly journals Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP/PS1 mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Haiwang Zhang ◽  
Youssif Ben Zablah ◽  
An Liu ◽  
Dongju Lee ◽  
Haorui Zhang ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Cell Types ◽  
Long Term Potentiation ◽  
Social Recognition ◽  
Cofilin Phosphorylation ◽  
Term Potentiation ◽  
Excitatory Neurons ◽  
Local Injections ◽  
The Brain

AbstractAccumulating evidence indicates that the actin regulator cofilin is overactivated in Alzheimer’s Disease (AD), but whether this abnormality contributes to synaptic and cognitive impairments in AD is unclear. In addition, the brain region and cell types involved remain unknown. In this study, we specifically manipulate LIMK1, the key protein kinase that phosphorylates and inactivates cofilin, in the hippocampus of APP/PS1 transgenic mice. Using local injections of the AAV virus containing LIMK1 under the control of the CaMKIIα promoter, we show that expression of LIMK1 in hippocampal excitatory neurons increases cofilin phosphorylation (i.e., decreases cofilin activity), rescues impairments in long-term potentiation, and improves social memory in APP/PS1 mice. Our results suggest that deficits in LIMK1/cofilin signaling in the hippocampal excitatory neurons contribute to AD pathology and that manipulations of LIMK1/cofilin activity provide a potential therapeutic strategy to treat AD.

Neurotrophins and Proneurotrophins: Focus on Synaptic Activity and Plasticity in the Brain

2017 ◽  
Vol 23 (6) ◽  
pp. 587-604 ◽  
Author(s):  
Julien Gibon ◽  
Philip A. Barker
Keyword(s):  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Neurotrophin 3 ◽  
New Findings ◽  
The Central Nervous System ◽  
The Brain

Neurotrophins have been intensively studied and have multiple roles in the brain. Neurotrophins are first synthetized as proneurotrophins and then cleaved intracellularly and extracellularly. Increasing evidences demonstrate that proneurotrophins and mature neurotrophins exerts opposing role in the central nervous system. In the present review, we explore the role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) and their respective proform in cellular processes related to learning and memory. We focused on their roles in synaptic activity and plasticity in the brain with an emphasis on long-term potentiation, long-term depression, and basal synaptic transmission in the hippocampus and the temporal lobe area. We also discuss new findings on the role of the Val66Met polymorphism on the BDNF propeptide on synaptic activity.

Priming-Induced Shift in Synaptic Plasticity in the Rat Hippocampus

1999 ◽  
Vol 82 (4) ◽  
pp. 2024-2028 ◽  
Author(s):  
Hongyan Wang ◽  
John J. Wagner
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Crossover Point ◽  
Term Potentiation ◽  
Before And After ◽  
History Of ◽  
The Brain ◽  
Dependent Mechanism

The activity history of a given neuron has been suggested to influence its future responses to synaptic input in one prominent model of experience-dependent synaptic plasticity proposed by Bienenstock, Cooper, and Munro (BCM theory). Because plasticity of synaptic plasticity (i.e., metaplasticity) is similar in concept to aspects of the BCM proposal, we have tested the possibility that a form of metaplasticity induced by a priming stimulation protocol might exhibit BCM-like characteristics. CA1 field excitatory postsynaptic potentials (EPSPs) obtained from rat hippocampal slices were used to monitor synaptic responses before and after conditioning stimuli (3–100 Hz) of the Schaffer collateral inputs. A substantial rightward shift (>5-fold) in the frequency threshold between long-term depression (LTD) and long-term potentiation (LTP) was observed <1 h after priming. This change in the LTD/P crossover point occurred at both primed and unprimed synaptic pathways. These results provide new support for the existence of a rapid, heterosynaptic, experience-dependent mechanism that is capable of modifying the synaptic plasticity phenomena that are commonly proposed to be important for developmental and learning/memory processes in the brain.

Calpains: Master Regulators of Synaptic Plasticity

2016 ◽  
Vol 23 (3) ◽  
pp. 221-231 ◽  
Author(s):  
Victor Briz ◽  
Michel Baudry
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Long Term Potentiation ◽  
Cytoskeletal Proteins ◽  
Local Protein Synthesis ◽  
Term Potentiation ◽  
Calpain 2 ◽  
The Brain ◽  
Local Protein

Although calpain was proposed to participate in synaptic plasticity and learning and memory more than 30 years ago, the mechanisms underlying its activation and the roles of different substrates have remained elusive. Recent findings have provided evidence that the two major calpain isoforms in the brain, calpain-1 and calpain-2, play opposite functions in synaptic plasticity. In particular, while calpain-1 activation is the initial trigger for certain forms of synaptic plasticity, that is, long-term potentiation, calpain-2 activation restricts the extent of plasticity. Moreover, while calpain-1 rapidly cleaves regulatory and cytoskeletal proteins, calpain-2-mediated stimulation of local protein synthesis reestablishes protein homeostasis. These findings have important implications for our understanding of learning and memory and disorders associated with impairment in these processes.

Klk8, a multifunctional protease in the brain and skin: analysis of knockout mice

2010 ◽  
Vol 391 (4) ◽  
Author(s):  
Shigetaka Yoshida
Keyword(s):  
Central Nervous System ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
The Central Nervous System ◽  
Synaptic Changes ◽  
Adhesive Molecules ◽  
High Level ◽  
Activity Dependent ◽  
The Brain

Abstract Klk8 is a tryptic serine protease with limited substrate specificity. Klk8 mRNA is expressed in many developing organs, whereas its expression is confined to limited regions, including the hippocampus, in adults. In the hippocampus, Klk8 is involved in activity-dependent synaptic changes such as long-term potentiation, which was found to be suppressed in Klk8 knockout (KO) mice. Oligodendrocytes only expressed Klk8 mRNA after injury to the central nervous system. The epidermis of the skin is one of the tissues that exhibits a high level of KLK8 expression. Klk8 might be involved in desquamation through the degradation of adhesive molecules that connect layers of the epidermis. Klk8 might thus be involved in tissue development and rearrangement.

scholarly journals Modelling thalamocortical circuitry shows visually induced LTP changes laminar connectivity in human visual cortex

2020 ◽  
Author(s):  
Rachael L. Sumner ◽  
Meg J. Spriggs ◽  
Alexander D. Shaw
Keyword(s):  
Visual Cortex ◽  
Computational Model ◽  
Evoked Potential ◽  
Long Term Potentiation ◽  
The State ◽  
Clinical Neuroscience ◽  
Non Invasive ◽  
Term Potentiation ◽  
The Brain

AbstractNeuroplasticity is essential to learning and memory in the brain; it has therefore also been implicated in numerous neurological and psychiatric disorders, making measuring the state of neuroplasticity of foremost importance to clinical neuroscience. Long-term potentiation (LTP) is a key mechanism of neuroplasticity and has been studied extensively, and invasively in non-human animals. Translation to human application largely relies on the validation of non-invasive measures of LTP. The current study provides validation for the use of a thalamocortical computational model of visual cortex for investigating and replicating interlaminar connectivity changes using non-invasive EEG recording of humans, and a commonly used visual sensory LTP paradigm. The model demonstrated remarkable accuracy recapitulating post-tetanus changes including increased excitatory connectivity from thalamus to layer IV and from layer IV to II/III. The findings also further validate visual sensory induced LTP and evoked potential modulation for measuring of the state of LTP in cortex.

scholarly journals Prolonged Systemic Inflammation Alters Muscarinic Long-Term Potentiation (mLTP) in the Hippocampus

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Efrat Shavit-Stein ◽  
Amir Dori ◽  
Marina Ben Shimon ◽  
Shany Guly Gofrit ◽  
Nicola Maggio
Keyword(s):  
Cognitive Impairment ◽  
Systemic Inflammation ◽  
Long Term Potentiation ◽  
Short Exposure ◽  
Short Term ◽  
Cholinergic Dysfunction ◽  
Term Potentiation ◽  
Hippocampal Synapses ◽  
The Brain

The cholinergic system plays a fundamental role in learning and memory. Pharmacological activation of the muscarinic receptor M1R potentiates NMDA receptor activity and induces short-term potentiation at the synapses called muscarinic LTP, mLTP. Dysfunction of cholinergic transmission has been detected in the settings of cognitive impairment and dementia. Systemic inflammation as well as neuroinflammation has been shown to profoundly alter synaptic transmission and LTP. Indeed, intervention which is aimed at reducing neuroinflammatory changes in the brain has been associated with an improvement in cognitive functions. While cognitive impairment caused either by cholinergic dysfunction and/or by systemic inflammation suggests a possible connection between the two, so far whether systemic inflammation affects mLTP has not been extensively studied. In the present work, we explored whether an acute versus persistent systemic inflammation induced by LPS injections would differently affect the ability of hippocampal synapses to undergo mLTP. Interestingly, while a short exposure to LPS resulted in a transient deficit in mLTP expression, a longer exposure persistently impaired mLTP. We believe that these findings may be involved in cognitive dysfunctions following sepsis and possibly neuroinflammatory processes.

Long-Term Potentiation and Long-Term Depression

2018 ◽  
Author(s):  
Arianna Maffei
Keyword(s):  
Synaptic Plasticity ◽  
Neural Circuit ◽  
Long Term Potentiation ◽  
Synaptic Connections ◽  
Long Term Depression ◽  
Term Potentiation ◽  
Functional Implications ◽  
The Brain

Synaptic connections in the brain can change their strength in response to patterned activity. This ability of synapses is defined as synaptic plasticity. Long lasting forms of synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD), are thought to mediate the storage of information about stimuli or features of stimuli in a neural circuit. Since its discovery in the early 1970s, synaptic plasticity became a central subject of neuroscience, and many studies centered on understanding its mechanisms, as well as its functional implications.

Enhancement of neuroplasticity by cortical stimulation

2020 ◽  
pp. 199-220
Author(s):  
Orlando B.C. Swayne ◽  
John C. Rothwell
Keyword(s):  
Clinical Trials ◽  
Neurological Disease ◽  
Magnetic Stimulation ◽  
Long Term Potentiation ◽  
Response To Therapy ◽  
Non Invasive ◽  
Term Potentiation ◽  
The Face ◽  
The Brain

Non-invasive brain stimulation methods such as transcranial magnetic stimulation and transcranial direct current stimulation allow us to interact directly with activity in neural circuits in the brain. Work has shown that these methods can also lead to changes in the effectiveness of synaptic connections, probably through mechanisms related to long-term potentiation/depression as described in animal preparations. Similar processes of synaptic plasticity are involved in many neurological rehabilitation techniques involve learning how to optimize performance in the face of neurological disease or injury. Thus combining non-invasive stimulation with rehabilitation may therefore be able to enhance plasticity and speed the response to therapy. We describe the techniques involved and summarize some of the recent clinical trials that have been conducted using this approach.

scholarly journals Aging and Synaptic Plasticity: A Review

2002 ◽  
Vol 9 (4) ◽  
pp. 217-232 ◽  
Author(s):  
Jorge A. Bergado ◽  
William Almaguer
Keyword(s):  
Neural Plasticity ◽  
Brain Aging ◽  
Long Term Potentiation ◽  
Causal Link ◽  
Term Potentiation ◽  
Gradual Loss ◽  
Age Dependent ◽  
Affective Influences ◽  
The Brain

Aging affects all systems, but the brain seems to be particularly vulnerable to the action of negative, age-dependent factors. A gradual loss of memory functions is one of the earliest and most widespread consequences of brain aging. The causes for such impairment are still unclear. Long-term potentiation (LTP) is one form of neural plasticity, which has been proposed as the cellular correlate for memory. LTP is affected by aging, and such alteration might be causally related to memory dysfunction. In the present paper, we review the evidence sustaining the existence of a causal link between cognitive and LTP impairments, as well as the possible mechanisms involved. New results indicate a possible involvement of a deficient reinforcement of LTP by affective influences.

scholarly journals Cell type-specific plasticity at parallel fiber synapses onto Purkinje cells in the posterior caudal lobe of the mormyrid fish cerebellum

2018 ◽  
Vol 120 (2) ◽  
pp. 644-661
Author(s):  
Yueping Zhang ◽  
Gerhard Magnus ◽  
Victor Z. Han
Keyword(s):  
Purkinje Cells ◽  
Cell Types ◽  
Long Term Potentiation ◽  
Cell Type ◽  
Long Term Depression ◽  
Caudal Lobe ◽  
Term Potentiation ◽  
Mormyrid Fish ◽  
Cell Type Specific

It has been demonstrated that there are two morphological subtypes of Purkinje cells (PCs)—fan-shaped Purkinje cells (fPCs) and multipolar Purkinje cells (mPCs)—in the posterior caudal lobe of the mormyrid fish cerebellum, but whether these cell types are also functionally distinct is unknown. Here, we have used electrophysiological and pharmacological tools in a slice preparation to demonstrate that pairing parallel fiber (PF) and climbing fiber (CF) inputs at a low frequency induces long-term depression (LTD) in fPCs but long-term potentiation (LTP) in mPCs. The induction of plasticity in both cell types required postsynaptic Ca2+ and type 1α metabotropic glutamate receptors. However, the LTD in fPCs was inducted via a calcium/calmodulin-dependent protein kinase II cascade, whereas LTP induction in mPCs required calcineurin. Moreover, the LTD in fPCs and LTP in mPCs were accompanied by changes to the corresponding paired-pulse ratios and their coefficients of variation, suggesting presynaptic modes of expression for the plasticity at PF terminals for both cell types. Hence, the synaptic plasticity at PF synapses onto PCs in the posterior caudal lobe of the mormyrid cerebellum is cell type specific, with both pre- and postsynaptic mechanisms contributing to its induction and expression. NEW & NOTEWORTHY Much has been learnt about the cerebellar long-term depression (LTD) in the cortex. More recent work has shown that long-term potentiation (LTP) is equally important for cerebellar motor learning. Here we report for the first time that plasticity in the mormyrid cerebellum is cell type specific, e.g., following the conventional pairing of parallel and climbing fiber inputs in an in vitro preparation leads to LTD in one Purkinje cell subtype and LTP in another.

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