scholarly journals Ablation of STAT3 in Purkinje Cells Reorganizes Cerebellar Synaptic Plasticity in Long-Term Fear Memory Network

2020 ◽  
Author(s):  
Jeong-Kyu Han ◽  
Sun-Ho Kwon ◽  
Yong Gyu Kim ◽  
Jaeyong Choi ◽  
Jong-Il Kim ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Emotional Memory ◽  
Brain Regions ◽  
Parallel Fiber ◽  
Wild Type ◽  
Memory Processing ◽  
Memory Network

Emotional memory processing, such as fear memory, engages a large neuronal network of brain regions including the cerebellum. However, the molecular and cellular mechanisms of the cerebellar cortex modulating the fear memory network is largely unknown. Here, we illustrate a novel mechanism by which synaptic signaling in cerebellar Purkinje cells (PCs) via STAT3 regulates long-term fear memory. Firstly, we generated PC-specific STAT3 knockout (STAT3PKO) mice. Transcriptome analyses revealed that STAT3 deletion results in transcriptional changes that lead to an increase in the expression of glutamate receptors. The amplitude of AMPA receptor-mediated excitatory postsynaptic currents at parallel fiber to PC synapses was larger in STAT3PKO mice than in wild-type littermates. Conditioning at the parallel fiber induced long-term depression of parallel fiber-PC synapses in STAT3PKO mice while the same manipulation induced long-term potentiation in wild-type littermates. Interestingly, STAT3PKO mice showed an aberrantly enhanced long-term fear memory. Neuronal activity in fear-related regions increased in fear-conditioned STAT3PKO mice. Our data suggest that STAT3-dependent molecular regulation in PCs is indispensable for proper expression of fear memory processing.

scholarly journals Ablation of STAT3 in Purkinje cells reorganizes cerebellar synaptic plasticity in long-term fear memory network

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jeong-Kyu Han ◽  
Sun-Ho Kwon ◽  
Yong Gyu Kim ◽  
Jaeyong Choi ◽  
Jong-Il Kim ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Emotional Memory ◽  
Brain Regions ◽  
Cellular Mechanisms ◽  
Term Potentiation ◽  
Memory Network ◽  
Cerebellar Purkinje Cells

Emotional memory processing engages a large neuronal network of brain regions including the cerebellum. However, the molecular and cellular mechanisms of the cerebellar cortex modulating the fear memory network are unclear. Here, we illustrate that synaptic signaling in cerebellar Purkinje cells (PCs) via STAT3 regulates long-term fear memory. Transcriptome analyses revealed that PC-specific STAT3 knockout (STAT3PKO) results in transcriptional changes that lead to an increase in the expression of glutamate receptors. The amplitude of AMPA receptor-mediated excitatory postsynaptic currents at parallel fiber (PF) to PC synapses was larger in STAT3PKO mice than in wild-type (WT) littermates. Fear conditioning induced long-term depression of PF–PC synapses in STAT3PKO mice while the same manipulation induced long-term potentiation in WT littermates. STAT3PKO mice showed an aberrantly enhanced long-term fear memory. Neuronal activity in fear-related regions increased in fear-conditioned STAT3PKO mice. Our data suggest that STAT3-dependent molecular regulation in PCs is indispensable for proper expression of fear memory.

Evidence for the Role of Endogenous Carbon Monoxide in Memory Processing

2007 ◽  
Vol 19 (4) ◽  
pp. 557-562 ◽  
Author(s):  
M. C. Cutajar ◽  
T. M. Edwards
Keyword(s):  
Carbon Monoxide ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
Memory Research ◽  
Memory Processing ◽  
Important Target ◽  
Term Potentiation ◽  
Per Se

For a decade and a half, nitric oxide (NO) has been implicated in memory processing across a wide variety of tasks and species. Comparatively, endogenously produced carbon monoxide (CO) has lagged behind as a target for research into the pharmacological processes underlying memory formation. This is surprising given that CO is formed in memory-associated brain regions, is structurally similar to NO, and along with NO can activate guanylate cyclase, which is an enzyme well characterized in memory processing. Nevertheless, a limited number of electrophysiological investigations have concluded that endogenous CO is involved in long-term potentiation. Although not evidence for a role in memory per se, these studies did point to the possible importance of CO in memory processing. In addition, there is now evidence to suggest that endogenous CO is important in avoidance learning and possible for other tasks. This review therefore seeks to promote endogenous CO as a potentially important target for memory research.

scholarly journals The 4-(Phenylsulfanyl) butan-2-one Improves Impaired Fear Memory Retrieval and Reduces Excessive Inflammatory Response in Triple Transgenic Alzheimer's Disease Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Peeraporn Varinthra ◽  
Kiruthika Ganesan ◽  
Shun-Ping Huang ◽  
Supin Chompoopong ◽  
Chatchakorn Eurtivong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Response ◽  
Memory Retrieval ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Emotional Memory ◽  
Therapeutic Drug ◽  
Wild Type ◽  
Excessive Inflammatory Response

Alzheimer's disease (AD) is a neurodegenerative disease characterized by an excessive inflammatory response and impaired memory retrieval, including spatial memory, recognition memory, and emotional memory. Acquisition and retrieval of fear memory help one avoid dangers and natural threats. Thus, it is crucial for survival. AD patients with impaired retrieval of fear memory are vulnerable to dangerous conditions. Excessive expression of inflammatory markers is known to impede synaptic transmission and reduce the efficiency of memory retrieval. In wild-type mice, reducing inflammation response can improve fear memory retrieval; however, this effect of this approach is not yet investigated in 3xTg-AD model mice. To date, no satisfactory drug or treatment can attenuate the symptoms of AD despite numerous efforts. In the past few years, the direction of therapeutic drug development for AD has been shifted to natural compounds with anti-inflammatory effect. In the present study, we demonstrate that the compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) is effective in enhancing fear memory retrieval of wild-type and 3xTg-AD mice by reducing the expression of TNF-α, COX-2, and iNOS. We also found that 4-PSB-2 helps increase dendritic spine density, postsynaptic density protein-95 (PSD-95) expression, and long-term potentiation (LTP) in the hippocampus of 3xTg-AD mice. Our study indicates that 4-PSB-2 may be developed as a promising therapeutic compound for treating fear memory impairment of AD patients.

scholarly journals Intrinsic Plasticity Complements Long-Term Potentiation in Parallel Fiber Input Gain Control in Cerebellar Purkinje Cells

2010 ◽  
Vol 30 (41) ◽  
pp. 13630-13643 ◽  
Author(s):  
A. Belmeguenai ◽  
E. Hosy ◽  
F. Bengtsson ◽  
C. M. Pedroarena ◽  
C. Piochon ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Gain Control ◽  
Long Term Potentiation ◽  
Parallel Fiber ◽  
Term Potentiation ◽  
Input Gain ◽  
Intrinsic Plasticity ◽  
Cerebellar Purkinje Cells

scholarly journals Memory Consolidation for Contextual and Auditory Fear Conditioning Is Dependent on Protein Synthesis, PKA, and MAP Kinase

1999 ◽  
Vol 6 (2) ◽  
pp. 97-110 ◽  
Author(s):  
Glenn E. Schafe ◽  
Nicole V. Nadel ◽  
Gregory M. Sullivan ◽  
Alexander Harris ◽  
Joseph E. LeDoux
Keyword(s):  
Protein Synthesis ◽  
Map Kinase ◽  
Fear Conditioning ◽  
Memory Consolidation ◽  
Molecular Mechanisms ◽  
Short Term Memory ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Term Memory

Fear conditioning has received extensive experimental attention. However, little is known about the molecular mechanisms that underlie fear memory consolidation. Previous studies have shown that long-term potentiation (LTP) exists in pathways known to be relevant to fear conditioning and that fear conditioning modifies neural processing in these pathways in a manner similar to LTP induction. The present experiments examined whether inhibition of protein synthesis, PKA, and MAP kinase activity, treatments that block LTP, also interfere with the consolidation of fear conditioning. Rats were injected intraventricularly with Anisomycin (100 or 300 μg), Rp-cAMPS (90 or 180 μg), or PD098059 (1 or 3 μg) prior to conditioning and assessed for retention of contextual and auditory fear memory both within an hour and 24 hr later. Results indicated that injection of these compounds selectively interfered with long-term memory for contextual and auditory fear, while leaving short-term memory intact. Additional control groups indicated that this effect was likely due to impaired memory consolidation rather than to nonspecific effects of the drugs on fear expression. Results suggest that fear conditioning and LTP may share common molecular mechanisms.

scholarly journals Emerging Link between Alzheimer’s Disease and Homeostatic Synaptic Plasticity

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Sung-Soo Jang ◽  
Hee Jung Chung
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Senile Plaques ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
Synaptic Activity ◽  
Homeostatic Plasticity ◽  
Brain Disorder

Alzheimer’s disease (AD) is an irreversible brain disorder characterized by progressive cognitive decline and neurodegeneration of brain regions that are crucial for learning and memory. Although intracellular neurofibrillary tangles and extracellular senile plaques, composed of insoluble amyloid-β(Aβ) peptides, have been the hallmarks of postmortem AD brains, memory impairment in early AD correlates better with pathological accumulation of soluble Aβoligomers and persistent weakening of excitatory synaptic strength, which is demonstrated by inhibition of long-term potentiation, enhancement of long-term depression, and loss of synapses. However, current, approved interventions aiming to reduce Aβlevels have failed to retard disease progression; this has led to a pressing need to identify and target alternative pathogenic mechanisms of AD. Recently, it has been suggested that the disruption of Hebbian synaptic plasticity in AD is due to aberrant metaplasticity, which is a form of homeostatic plasticity that tunes the magnitude and direction of future synaptic plasticity based on previous neuronal or synaptic activity. This review examines emerging evidence for aberrant metaplasticity in AD. Putative mechanisms underlying aberrant metaplasticity in AD will also be discussed. We hope this review inspires future studies to test the extent to which these mechanisms contribute to the etiology of AD and offer therapeutic targets.

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.

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