A5058252786- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Receptor Mechanisms and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Photoreceptor and optogenetics research
- Neuroendocrine regulation and behavior
- Nuclear Receptors and Signaling
- Neural dynamics and brain function
- Nerve injury and regeneration
- Stress Responses and Cortisol
- Sleep and Wakefulness Research
- Nicotinic Acetylcholine Receptors Study
- Histone Deacetylase Inhibitors Research
- Ion channel regulation and function
- Phosphodiesterase function and regulation
- Epigenetics and DNA Methylation
- Tryptophan and brain disorders
- Neuroscience and Neural Engineering
- Retinal Development and Disorders
- Neuroscience, Education and Cognitive Function
- Mitochondrial Function and Pathology
- Trace Elements in Health
National University of Singapore
2016-2025
Institute for Basic Science
2022
National University Health System
2019
Technische Universität Braunschweig
2010-2017
Duke-NUS Medical School
2016
Leibniz Institute for Neurobiology
2003-2010
Singapore General Hospital
2009
Institute of Nuclear Medicine & Allied Sciences
2002-2003
Although the maintenance mechanism of late long-term potentiation (LTP) is critical for storage memory, expression synaptic enhancement during late-LTP unknown. The autonomously active protein kinase C isoform, Mζ (PKMζ), a core molecule maintaining late-LTP. Here we show that PKMζ maintains through persistent N -ethylmaleimide-sensitive factor (NSF)/glutamate receptor subunit 2 (GluR2)-dependent trafficking AMPA receptors (AMPARs) to synapse. Intracellular perfusion into CA1 pyramidal cells...
Protein kinase Mζ (PKMζ) is a persistently active protein C isoform that synthesized during long-term potentiation (LTP) and critical for maintaining LTP. According to "synaptic tagging," newly synthesized, functionally important plasticity-related proteins (PRPs) may prolong not only at strongly tetanized pathways, but also independent, weakly pathways if synaptic tags are set. We therefore investigated whether PKMζ involved in tagging contributes sustained by providing strong weak...
Protein synthesis-dependent forms of hippocampal long-term potentiation (late LTP) and depression LTD) are prominent cellular mechanisms underlying memory formation. Recent data support the hypothesis that neurons store relevant information in dendritic functional compartments during late LTP LTD rather than single synapses. It has been suggested processes "synaptic tagging" restricted to such compartments. Here, we show addition apical CA1 dendrites, synaptic tagging also takes place within...
Activity-dependent synaptic plasticity is widely accepted to be the cellular correlate of learning and memory. It believed that associativity between different inputs can transform short-lasting forms (<3 h) long-lasting ones. Synaptic tagging capture (STC) might able explain this heterosynaptic support, because it distinguishes local mechanisms tags cell-wide responsible for synthesis plasticity-related proteins (PRPs). STC initiate storage processes only when strength tag concentration...
The tuberal nucleus (TN) is a surprisingly understudied brain region. We found that somatostatin (SST) neurons in the TN, which known to exhibit pathological or cytological changes human neurodegenerative diseases, play crucial role regulating feeding mice. GABAergic SST (TNSST) were activated by hunger and hormone, ghrelin. Activation of TNSST promoted feeding, whereas inhibition reduced it via projections paraventricular bed stria terminalis. Ablation body weight gain food intake. These...
Recent findings point to a central role of the endoplasmic reticulum-resident STIM (Stromal Interaction Molecule) proteins in shaping structure and function excitatory synapses mammalian brain. The impact Stim genes on cognitive functions remains, however, poorly understood. To explore learning memory, we generated three mouse strains with conditional deletion (cKO) Stim1 and/or Stim2 forebrain. Stim1, Stim2, double Stim1/Stim2 cKO mice show no obvious brain structural defects or locomotor...
Canonical models suggest that mechanisms of long-term memory consist a synapse-specific, protein synthesis-independent induction phase (changes in synaptic weights/temporary tagging such synapses) and, within adjacent dendritic compartments, synthesis-dependent distribution may accompany or immediately precede and whose products enable consolidation through capture. We now report this is competitive "winner-take-all" fashion when synapses potentiated at compete with each other for...
Abstract Progressive memory loss is one of the most common characteristics Alzheimer's disease (AD), which has been shown to be caused by several factors including accumulation amyloid β peptide (Aβ) plaques and neurofibrillary tangles. Synaptic plasticity associative plasticity, cellular basis memory, are impaired in AD. Recent studies suggest a functional relevance microRNAs (miRNAs) regulating changes AD, as their differential expressions were reported many AD brain regions. However,...
Abstract Microglia are the main form of immune defense in central nervous system. express phosphatidylinositol 3‐kinase (PI3K), which has been shown to play a significant role synaptic plasticity neurons and inflammation via microglia. This study shows that microglial PI3K is regulated epigenetically through histone modifications posttranslationally sumoylation involved long‐term potentiation (LTP) by modulating expression brain‐derived neurotrophic factor (BDNF), be neuronal plasticity....
Sleep deprivation (SD) interferes with hippocampal structural and functional plasticity, formation of long-term memory cognitive function. The molecular mechanisms underlying these effects are incompletely understood. Here, we show that SD impaired synaptic tagging capture behavioral tagging, two major associative learning memory. Strikingly, mutant male mice lacking the p75 neurotrophin receptor (p75<sup>NTR</sup>) were resistant to detrimental on plasticity at both cellular levels....
The plasticity mechanisms in the nervous system that are important for learning and memory greatly impacted during aging. Notably, hippocampal-dependent long-term its associative plasticity, such as synaptic tagging capture (STC), show considerable age-related decline. p75 neurotrophin receptor (p75NTR ) is a negative regulator of structural functional brain thus represents potential candidate to mediate alterations. However, by which p75NTR affects aged neuronal networks ultimately...
We investigated the effects of rolipram, a selective cAMP phosphodiesterase (PDE) inhibitor, on late plastic events during functional CA1 plasticity in vitro rat hippocampal slices. present data showing that an early form long-term potentiation (LTP) (early-LTP) normally decays within 2-3 hr can be converted to lasting LTP (late-LTP) if rolipram is applied tetanization. This rolipram-reinforced (RLTP) was NMDA receptor and protein synthesis dependent. formation region late-LTP requires...
Activity-dependent changes in synaptic strength such as long-term potentiation (LTP) and depression (LTD) are considered to be cellular mechanisms underlying learning memory. Strengthening of a synapse for few seconds or minutes is termed short-term (STP) normally unable take part the processes tagging/capture due its inability set “synaptic tags.” Here, we report that priming synapses with ryanodine receptor agonists (10 μM) caffeine mM) facilitates subsequent tagging/capture, enabling an...
One conceptual mechanism for the induction of associative long-term memory is that a synaptic tag, set by weak event, can capture plasticity-related proteins from nearby strong input, thus enabling associativity between 2 (synaptic tagging and capture, STC). So far, STC has been observed only limited time 60 min. Nevertheless, association forms occur beyond this period its not well understood. Here we report metaplasticity induced ryanodine receptor activation or metabotropic glutamate...
Neurodegenerative diseases such as Alzheimer's disease (AD) are associated with alterations in epigenetic factors leading to cognitive decline. Histone deacetylase 3 (HDAC3) is a known critical negative regulator of learning and memory. In this study, attenuation long-term potentiatio n by amyloid-β oligomer, its reversal specific HDAC3 inhibitor RGFP966, was performed rat CA1 pyramidal neurons using whole cell voltage-clamp field recording techniques. Our findings provide the first evidence...
Significance Under physiological conditions, metaplasticity is ideally suited to prepare neuronal networks for encoding specific information, thereby ensuring subsequent learning and long-lasting memory storage. Our capacity lies at the heart of all cognitive function, correct scaling synaptic plasticity vital normal brain function. Here we present data from amyloid precursor protein (APP)/presenilin-1 (PS1) mice, a mouse model Alzheimer’s disease, indicating that failure neurons scale...
Significance The hippocampal area Cornu Ammonis (CA) CA2 is a small region interposed between CA1 and CA3. For long time, there has been lack of information on the area’s role in memory formation. This innervated by supramammillary axonal fibers that are rich with Substance P (SP), which acts as neurotransmitter neuromodulator. We show SP induces an NMDA receptor- protein synthesis-dependent potentiation synapses requires kinases such CaMKIV PKMζ. SP-induced effects Schaffer collateral-CA2...
Abstract Aging is associated with impaired plasticity and memory. Altered epigenetic mechanisms are implicated in the impairment of memory advanced aging. Histone deacetylase 3 (HDAC3) an important negative regulator However, role HDAC3 aged neural networks not well established. Late long-term potentiation (late-LTP), a cellular correlate its associative such as synaptic tagging capture (STC) were studied CA1 area hippocampal slices from 82–84 week old rats. Our findings demonstrate that...
Metabotropic glutamate receptors (mGluRs) play an important role in synaptic plasticity and memory are largely classified based on amino acid sequence homology pharmacological properties. Among group III metabotropic receptors, mGluR7 mGluR4 show high relative expression the rat hippocampal area CA2. Group known to down-regulate cAMP-dependent signaling pathways via activation of Gi/o proteins. Here, we provide evidence that inhibition mGluRs by specific antagonists permits NMDA receptor-...