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.

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.

scholarly journals Synaptic Plasticity and its Modulation by Alcohol

2020 ◽  
Vol 6 (1) ◽  
pp. 103-111 ◽  
Author(s):  
Yosef Avchalumov ◽  
Chitra D. Mandyam
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Dorsal Striatum ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
Public Health Issue ◽  
Cellular Mechanisms ◽  
Brain Disorder ◽  
The Brain

Alcohol is one of the oldest pharmacological agents used for its sedative/hypnotic effects, and alcohol abuse and alcohol use disorder (AUD) continues to be major public health issue. AUD is strongly indicated to be a brain disorder, and the molecular and cellular mechanism/s by which alcohol produces its effects in the brain are only now beginning to be understood. In the brain, synaptic plasticity or strengthening or weakening of synapses, can be enhanced or reduced by a variety of stimulation paradigms. Synaptic plasticity is thought to be responsible for important processes involved in the cellular mechanisms of learning and memory. Long-term potentiation (LTP) is a form of synaptic plasticity, and occurs via N-methyl-D-aspartate type glutamate receptor (NMDAR or GluN) dependent and independent mechanisms. In particular, NMDARs are a major target of alcohol, and are implicated in different types of learning and memory. Therefore, understanding the effect of alcohol on synaptic plasticity and transmission mediated by glutamatergic signaling is becoming important, and this will help us understand the significant contribution of the glutamatergic system in AUD. In the first part of this review, we will briefly discuss the mechanisms underlying long term synaptic plasticity in the dorsal striatum, neocortex and the hippocampus. In the second part we will discuss how alcohol (ethanol, EtOH) can modulate long term synaptic plasticity in these three brain regions, mainly from neurophysiological and electrophysiological studies. Taken together, understanding the mechanism(s) underlying alcohol induced changes in brain function may lead to the development of more effective therapeutic agents to reduce AUDs.

scholarly journals Endocannabinoid dynamics gate spike-timing dependent depression and potentiation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Yihui Cui ◽  
Ilya Prokin ◽  
Hao Xu ◽  
Bruno Delord ◽  
Stephane Genet ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Long Term Potentiation ◽  
Cellular Mechanism ◽  
Spike Timing ◽  
Long Term Depression ◽  
Term Potentiation ◽  
Short And Long Term

Synaptic plasticity is a cardinal cellular mechanism for learning and memory. The endocannabinoid (eCB) system has emerged as a pivotal pathway for synaptic plasticity because of its widely characterized ability to depress synaptic transmission on short- and long-term scales. Recent reports indicate that eCBs also mediate potentiation of the synapse. However, it is not known how eCB signaling may support bidirectionality. Here, we combined electrophysiology experiments with mathematical modeling to question the mechanisms of eCB bidirectionality in spike-timing dependent plasticity (STDP) at corticostriatal synapses. We demonstrate that STDP outcome is controlled by eCB levels and dynamics: prolonged and moderate levels of eCB lead to eCB-mediated long-term depression (eCB-tLTD) while short and large eCB transients produce eCB-mediated long-term potentiation (eCB-tLTP). Moreover, we show that eCB-tLTD requires active calcineurin whereas eCB-tLTP necessitates the activity of presynaptic PKA. Therefore, just like glutamate or GABA, eCB form a bidirectional system to encode learning and memory.

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.

scholarly journals An Overview of the Involvement of D-Serine in Cognitive Impairment in Normal Aging and Dementia

2021 ◽  
Vol 12 ◽  
Author(s):  
Magdalena Orzylowski ◽  
Esther Fujiwara ◽  
Darrell D. Mousseau ◽  
Glen B. Baker
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Memory Loss ◽  
Long Term Potentiation ◽  
Normal Aging ◽  
Serine Racemase ◽  
Cognitive Deterioration ◽  
Term Potentiation ◽  
Potential Biomarker

Dementia, of which Alzheimer's disease (AD) is the most common form, is characterized by progressive cognitive deterioration, including profound memory loss, which affects functioning in many aspects of life. Although cognitive deterioration is relatively common in aging and aging is a risk factor for AD, the condition is not necessarily a part of the aging process. The N-methyl-D-aspartate glutamate receptor (NMDAR) and its co-agonist D-serine are currently of great interest as potential important contributors to cognitive function in normal aging and dementia. D-Serine is necessary for activation of the NMDAR and in maintenance of long-term potentiation (LTP) and is involved in brain development, neuronal connectivity, synaptic plasticity and regulation of learning and memory. In this paper, we review evidence, from both preclinical and human studies, on the involvement of D-serine (and the enzymes involved in its metabolism) in regulation of cognition. Potential mechanisms of action of D-serine are discussed in the context of normal aging and in dementia, as is the potential for using D-serine as a potential biomarker and/or therapeutic agent in dementia. Although there is some controversy in the literature, it has been proposed that in normal aging there is decreased expression of serine racemase and decreased levels of D-serine and down-regulation of NMDARs, resulting in impaired synaptic plasticity and deficits in learning and memory. In contrast, in AD there appears to be activation of serine racemase, increased levels of D-serine and overstimulation of NMDARs, resulting in cytotoxicity, synaptic deficits, and dementia.

scholarly journals Sex differences in spatial learning and memory and hippocampal long-term potentiation at perforant pathway-dentate gyrus (PP-DG) synapses in Wistar rats

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Samaneh Safari ◽  
Nesa Ahmadi ◽  
Reihaneh Mohammadkhani ◽  
Reza Ghahremani ◽  
Maryam Khajvand-Abedeni ◽  
...  
Keyword(s):  
Sex Differences ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Long Term Potentiation ◽  
Female Rats ◽  
Male Rats ◽  
Spatial Learning And Memory ◽  
Term Potentiation

Abstract Background Recent studies show that gender may have a significant impact on brain functions. However, the reports of sex effects on spatial ability and synaptic plasticity in rodents are divergent and controversial. Here spatial learning and memory was measured in male and female rats by using Morris water maze (MWM) task. Moreover, to assess sex difference in hippocampal synaptic plasticity we examined hippocampal long-term potentiation (LTP) at perforant pathway-dentate gyrus (PP-DG) synapses. Results In MWM task, male rats outperformed female rats, as they had significantly shorter swim distance and escape latency to find the hidden platform during training days. During spatial reference memory test, female rats spent less time and traveled less distance in the target zone. Male rats also had larger LTP at PP-DG synapses, which was evident in the high magnitude of population spike (PS) potentiation and the field excitatory post synaptic potentials (fEPSP) slope. Conclusions Taken together, our results suggest that sex differences in the LTP at PP-DG synapses, possibly contribute to the observed sex difference in spatial learning and memory.

scholarly journals Numerical Simulation: Fluctuation in Background Synaptic Activity Regulates Synaptic Plasticity

2021 ◽  
Vol 15 ◽  
Author(s):  
Yuto Takeda ◽  
Katsuhiko Hata ◽  
Tokio Yamazaki ◽  
Masaki Kaneko ◽  
Osamu Yokoi ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Statistical Fluctuation ◽  
Noisy Environment ◽  
Term Potentiation ◽  
Synapse Model ◽  
The Brain

Synaptic plasticity is vital for learning and memory in the brain. It consists of long-term potentiation (LTP) and long-term depression (LTD). Spike frequency is one of the major components of synaptic plasticity in the brain, a noisy environment. Recently, we mathematically analyzed the frequency-dependent synaptic plasticity (FDP) in vivo and found that LTP is more likely to occur with an increase in the frequency of background synaptic activity. Meanwhile, previous studies suggest statistical fluctuation in the amplitude of background synaptic activity. Little is understood, however, about its contribution to synaptic plasticity. To address this issue, we performed numerical simulations of a calcium-based synapse model. Then, we found attenuation of the tendency to become LTD due to an increase in the fluctuation of background synaptic activity, leading to an enhancement of synaptic weight. Our result suggests that the fluctuation affects synaptic plasticity in the brain.

scholarly journals Developmental onset of enduring long-term potentiation in mouse hippocampus

2019 ◽  
Author(s):  
Olga I. Ostrovskaya ◽  
Guan Cao ◽  
Cagla Eroglu ◽  
Kristen M. Harris
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Mouse Strains ◽  
Developmental Profile ◽  
Important Species ◽  
Term Potentiation ◽  
Mouse Hippocampus

ABSTRACTAnalysis of long-term potentiation (LTP) provides a powerful window into cellular mechanisms of learning and memory. Prior work shows late LTP (L-LTP), lasting >3 hours, occurs abruptly at postnatal day 12 (P12) in rat hippocampus. The goal here was to determine the developmental profile of synaptic plasticity leading to L-LTP in the mouse hippocampus. Two mouse strains and two mutations known to affect synaptic plasticity were chosen: C57BL/6 and Fmr1−/y on the C57BL/6 background, and 129SVE and Hevin−/− (Sparcl1−/−) on the 129SVE background. Like rats, hippocampal slices from all of the mice showed test pulse-induced depression early during development that was gradually resolved with maturation by 5 weeks. All the mouse strains showed a gradual progression between P10-P35 in the expression of short-term potentiation (STP), lasting ≤ one hour. In the 129SVE mice, L-LTP onset (>25% of slices) occurred by 3 weeks, reliable L-LTP (>50% slices) was achieved by 4 weeks, and Hevin−/− advanced this profile by one week. In the C57BL/6 mice, L-LTP onset occurred significantly later, over 3-4 weeks, and reliability was not achieved until 5 weeks. Although some of the Fmr1−/y mice showed L-LTP before 3 weeks, reliable L-LTP also was not achieved until 5 weeks. Two bouts of TBS separated by ≥90 minutes advanced the onset age of L-LTP in rats from P12 to P10. In contrast, L-LTP onset was not advanced in any of the mouse genotypes by multiple bouts of TBS at 90 or 180 minute intervals. These findings show important species differences in the onset of STP and L-LTP, which occur at the same age in rats but are sequentially acquired in mice.SIGNIFICANCE STATEMENTLong-term potentiation (LTP) is a cellular mechanism of learning and memory. Knowing the developmental profile for LTP provides a basis for investigating developmental abnormalities leading to intellectual disabilities and other neurodevelopmental disorders. Here we explore the developmental profile of LTP onset in two wild type mouse strains, C57BL/6 and 129SVE, together with Fmr1−/y and Hevin−/− (Sparcl1−/−) mutations that produce abnormalities in synaptic structure, plasticity, and development. Our data provide a foundation for future investigations into connections between structural and functional plasticity leading to developmental anomalies in the brain.

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