Widespread promoter methylation of synaptic plasticity genes in long-term potentiation in the adult brain in vivo

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

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Estrogenic Regulation of Synaptic Actin Proteins and Plasticity

Estrogens and Memory ◽

10.1093/oso/9780190645908.003.0006 ◽

2020 ◽

pp. 69-82

Author(s):

Enikö A. Kramár

Keyword(s):

Synaptic Plasticity ◽

Long Term Potentiation ◽

Synaptic Strength ◽

Adult Brain ◽

Actin Dynamics ◽

Signaling Cascade ◽

Term Potentiation ◽

Estrogenic Regulation ◽

Estradiol Levels

Estrogens are rapid and potent facilitators of synaptic plasticity in the adult brain; however, the steps that link estrogens to factors that regulate synaptic strength remain unclear. The present chapter will first review the acute effects of 17β‎-estradiol on synaptic transmission and long-term potentiation (LTP). It will then describe a synaptic model used to study the substrates of LTP and provide evidence for the ability of estradiol to rapidly engage a selective actin signaling cascade associated with the consolidation of LTP. Finally, it will be shown that chronic reductions in estradiol levels disrupt LTP and actin dynamics but can be reversed by acute infusions of the hormone. It is concluded here that estradiol can promote learning-related plasticity by modifying the synaptic cytoskeleton.

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Nicotine Enhances the Depressive Actions of Aβ1–40 on Long-Term Potentiation in the Rat Hippocampal CA1 Region In Vivo

Journal of Neurophysiology ◽

10.1152/jn.00996.2002 ◽

2003 ◽

Vol 89 (6) ◽

pp. 2917-2922 ◽

Cited By ~ 35

Author(s):

D. B. Freir ◽

C. E. Herron

Keyword(s):

Synaptic Plasticity ◽

Long Term Potentiation ◽

Α7 Nicotinic Acetylcholine Receptor ◽

High Affinity ◽

Ca1 Region ◽

Α7 Nachr ◽

Term Potentiation ◽

Significant Depression

Hippocampal long-term potentiation (LTP) is a form of synaptic plasticity used as a cellular model of memory. Beta amyloid (Aβ) is involved in Alzheimer's disease (AD), a neurode-generative disorder leading to cognitive deficits. Nicotine is also claimed to act as a cognitive enhancer. Aβ is known to bind with high affinity to the α7-nicotinic acetylcholine receptor (nAChR). Here we have investigated the effect of intracerebroventricular (icv) injection of the endogenous peptide Aβ1–40 on LTP in area CA1 of urethananesthetized rats. We also examined the effect of Aβ12–28 (icv), which binds with high affinity to the α7-nAChR and the specific α7-nAChR antagonist methyllycaconitine (MLA) on LTP. We found that Aβ12–28 had no effect on LTP, whereas MLA depressed significantly LTP, suggesting that activation of the α7-nAChR is a requirement for LTP. Within the in vivo environment, where other factors may compete with Aβ12–28 for binding to α7-nAChR, it does not appear to modulate LTP. To determine if the depressive action of Aβ1–40 on LTP could be modulated by nicotine, these agents were also co-applied. Injection of 1 or 10 nmol Aβ1–40 caused a significant depression of LTP, whereas nicotine alone (3 mg/kg) had no effect on LTP. Co-injection of nicotine with Aβ1–40 1 h prior to LTP induction caused a further significant depression of LTP compared with Aβ1–40 alone. These results demonstrate that nicotine enhances the deficit in LTP produced by Aβ1–40. This then suggests that nicotine may exacerbate the depressive actions of Aβ on synaptic plasticity in AD.

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Simvastatin Impairs Hippocampal Synaptic Plasticity and Cognitive Function in Mice

10.21203/rs.3.rs-76680/v2 ◽

2021 ◽

Author(s):

Yujun Guo ◽

Guichang Zou ◽

Keke Qi ◽

Jin Jin ◽

Lei Yao ◽

...

Keyword(s):

Synaptic Plasticity ◽

Memory Function ◽

Long Term Potentiation ◽

Drug Discontinuation ◽

Cholesterol Levels ◽

Hippocampal Synaptic Plasticity ◽

Term Potentiation ◽

The Central Nervous System

Abstract Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive

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Effects of the hydroalcoholic extract of Rosa damascena on hippocampal long-term potentiation in rats fed high-fat diet

The Journal of Physiological Sciences ◽

10.1186/s12576-021-00797-y ◽

2021 ◽

Vol 71 (1) ◽

Author(s):

Seyed Asaad Karimi ◽

Somayeh Komaki ◽

Masoumeh Taheri ◽

Ghazaleh Omidi ◽

Masoumeh Kourosh-Arami ◽

...

Keyword(s):

Synaptic Plasticity ◽

Long Term Potentiation ◽

Rosa Damascena ◽

High Fat ◽

Oxidative Stress Biomarkers ◽

Hydroalcoholic Extract ◽

Hippocampal Synaptic Plasticity ◽

Term Potentiation

AbstractHigh-fat diets (HFDs) and obesity can cause serious health problems, such as neurodegenerative diseases and cognitive impairments. Consumption of HFD is associated with reduction in hippocampal synaptic plasticity. Rosa damascena (R. damascena) is traditionally used as a dietary supplement for many disorders. This study was carried out to determine the beneficial effect of hydroalcoholic extract of R. damascena on in vivo hippocampal synaptic plasticity (long-term potentiation, LTP) in the perforant pathway (PP)—dentate gyrus (DG) pathway in rats fed with an HFD. Male Wistar rats were randomly assigned to four groups: Control, R. damascena extract (1 g/kg bw daily for 30 days), HFD (for 90 days) and HFD + extract. The population spike (PS) amplitude and slope of excitatory post-synaptic potentials (EPSP) were measured in DG area in response to stimulation applied to the PP. Serum oxidative stress biomarkers [total thiol group (TTG) and superoxide dismutase (SOD)] were measured. The results showed the HFD impaired LTP induction in the PP-DG synapses. This conclusion is supported by decreased EPSP slope and PS amplitude of LTP. R. damascena supplementation in HFD animals enhanced EPSP slope and PS amplitude of LTP in the granular cell of DG. Consumption of HFD decreased TTG and SOD. R. damascena extract consumption in the HFD animals enhanced TTG and SOD. These data indicate that R. damascena dietary supplementation can ameliorate HFD-induced alteration of synaptic plasticity, probably through its significant antioxidant effects and activate signalling pathways, which are critical in controlling synaptic plasticity.

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Irradiation of the Juvenile Brain Provokes a Shift from Long-Term Potentiation to Long-Term Depression

Developmental Neuroscience ◽

10.1159/000430435 ◽

2015 ◽

Vol 37 (3) ◽

pp. 263-272 ◽

Cited By ~ 4

Author(s):

Giulia Zanni ◽

Kai Zhou ◽

Ilse Riebe ◽

Cuicui Xie ◽

Changlian Zhu ◽

...

Keyword(s):

Synaptic Plasticity ◽

Young Patients ◽

Long Term Potentiation ◽

Hippocampal Neurogenesis ◽

Adult Brain ◽

High Frequency Stimulation ◽

Excitatory Postsynaptic Potential ◽

Long Term Depression ◽

Term Potentiation

Radiotherapy is common in the treatment of brain tumors in children but often causes deleterious, late-appearing sequelae, including cognitive decline. This is thought to be caused, at least partly, by the suppression of hippocampal neurogenesis. However, the changes in neuronal network properties in the dentate gyrus (DG) following the irradiation of the young, growing brain are still poorly understood. We characterized the long-lasting effects of irradiation on the electrophysiological properties of the DG after a single dose of 6-Gy whole-brain irradiation on postnatal day 11 in male Wistar rats. The assessment of the basal excitatory transmission in the medial perforant pathway (MPP) by an examination of the field excitatory postsynaptic potential/volley ratio showed an increase of the synaptic efficacy per axon in irradiated animals compared to sham controls. The paired-pulse ratio at the MPP granule cell synapses was not affected by irradiation, suggesting that the release probability of neurotransmitters was not altered. Surprisingly, the induction of long-term synaptic plasticity in the DG by applying 4 trains of high-frequency stimulation provoked a shift from long-term potentiation (LTP) to long-term depression (LTD) in irradiated animals compared to sham controls. The morphological changes consisted in a virtually complete ablation of neurogenesis following irradiation, as judged by doublecortin immunostaining, while the inhibitory network of parvalbumin interneurons was intact. These data suggest that the irradiation of the juvenile brain caused permanent changes in synaptic plasticity that would seem consistent with an impairment of declarative learning. Unlike in our previous study in mice, lithium treatment did unfortunately not ameliorate any of the studied parameters. For the first time, we show that the effects of cranial irradiation on long-term synaptic plasticity is different in the juvenile compared with the adult brain, such that while irradiation of the adult brain will only cause a reduction in LTP, irradiation of the juvenile brain goes further and causes LTD. Although the mechanisms underlying the synaptic alterations need to be elucidated, these findings provide a better understanding of the effects of irradiation in the developing brain and the cognitive deficits observed in young patients who have been subjected to cranial radiotherapy.

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Coincidence of cholinergic pauses, dopaminergic activation and depolarization drives synaptic plasticity in the striatum

10.1101/803536 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yan-Feng Zhang ◽

Simon D. Fisher ◽

Manfred Oswald ◽

Jeffery R. Wickens ◽

John N. J. Reynolds

Keyword(s):

Synaptic Plasticity ◽

Reinforcement Learning ◽

Long Term Potentiation ◽

Dopamine Neurons ◽

Projection Neurons ◽

Cholinergic Interneurons ◽

Term Potentiation ◽

Phasic Activation

AbstractPauses in the firing of tonically-active cholinergic interneurons (ChIs) in the striatum coincide with phasic activation of dopamine neurons during reinforcement learning. However, how this pause influences cellular substrates of learning is unclear. Using two in vivo paradigms, we report that long-term potentiation (LTP) at corticostriatal synapses with spiny projection neurons (SPNs) is dependent on the temporal coincidence of ChI pause and dopamine phasic activation, critically accompanied by SPN depolarization.

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Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice

Molecular Brain ◽

10.1186/s13041-021-00758-x ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Yujun Guo ◽

Guichang Zou ◽

Keke Qi ◽

Jin Jin ◽

Lei Yao ◽

...

Keyword(s):

Synaptic Plasticity ◽

Cognitive Function ◽

Memory Function ◽

Long Term Potentiation ◽

Drug Discontinuation ◽

Hippocampal Synaptic Plasticity ◽

Term Potentiation ◽

The Central Nervous System

AbstractLipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive function impairment, caused by long-term usage of BBB-permeable statins.

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Simvastatin Impairs Hippocampal Synaptic Plasticity and Cognitive Function in Mice

10.21203/rs.3.rs-76680/v1 ◽

2020 ◽

Author(s):

Yujun Guo ◽

Guichang Zou ◽

Jin Jin ◽

Lei Yao ◽

Keke Qi ◽

...

Keyword(s):

Synaptic Plasticity ◽

Cognitive Function ◽

Memory Function ◽

Long Term Potentiation ◽

Drug Discontinuation ◽

Hippocampal Synaptic Plasticity ◽

Term Potentiation ◽

The Central Nervous System

Abstract Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive function impairment, caused by long-term usage of BBB-permeable statins.

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Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo

10.1101/763540 ◽

2019 ◽

Author(s):

Cleiton Lopes-Aguiar ◽

Rafael N. Ruggiero ◽

Matheus T. Rossignoli ◽

Ingrid de Miranda Esteves ◽

José Eduardo Peixoto Santos ◽

...

Keyword(s):

Prefrontal Cortex ◽

Synaptic Plasticity ◽

Animal Models ◽

Long Term Potentiation ◽

Brain Regions ◽

High Frequency Stimulation ◽

Evoked Responses ◽

Term Potentiation

ABSTRACTN-methyl-D-aspartate receptor (NMDAr) antagonists such as ketamine (KET) produce psychotic-like behavior in both humans and animal models. NMDAr hypofunction affects normal oscillatory dynamics and synaptic plasticity in key brain regions related with schizophrenia, particularly in the hippocampus and the prefrontal cortex. In contrast, long-term potentiation (LTP) induction is known to increase glutamatergic transmission. Thus, we hypothesized that LTP could mitigate the electrophysiological changes promoted by KET. We recorded HPC-PFC local field potentials and evoked responses in urethane anesthetized rats, before and after KET administration, preceded or not by LTP induction. Our results show that KET promotes an aberrant delta-high-gamma crossfrequency coupling in the PFC and an enhancement in HPC-PFC evoked responses. LTP induction prior to KET attenuates changes in synaptic efficiency and prevents the increase in cortical gamma amplitude comodulation. These findings are consistent with evidence that increased efficiency of glutamatergic receptors attenuates cognitive impairment in animal models of psychosis. Therefore, high-frequency stimulation in HPC may be a useful tool to better understand how to prevent NMDAr hypofunction effects on synaptic plasticity and oscillatory coordination in cortico-limbic circuits.

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