A5038189543- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Neural dynamics and brain function
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion channel regulation and function
- Photoreceptor and optogenetics research
- Receptor Mechanisms and Signaling
- Amino Acid Enzymes and Metabolism
- Mitochondrial Function and Pathology
- Epilepsy research and treatment
- Neuroendocrine regulation and behavior
- Tryptophan and brain disorders
- Nicotinic Acetylcholine Receptors Study
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Stress Responses and Cortisol
- Cancer, Hypoxia, and Metabolism
- Neurogenesis and neuroplasticity mechanisms
- Phosphodiesterase function and regulation
- Metabolomics and Mass Spectrometry Studies
- MicroRNA in disease regulation
- Retinal Development and Disorders
- Genetics and Neurodevelopmental Disorders
Lunenfeld-Tanenbaum Research Institute
2018-2024
Mount Sinai Hospital
2018-2024
Sinai Health System
2022-2024
University of Bristol
2006-2022
Seoul National University
2011-2022
At Bristol
2013
Eli Lilly (United Kingdom)
2011
Medical Research Council
2006
Two forms of long-term depression (LTD), triggered by activation NMDA receptors (NMDARs) and metabotropic glutamate (mGluRs), respectively, can be induced at CA1 synapses in the hippocampus. Compared with NMDAR-LTD, relatively little is known about mGluR-LTD. Here, we show that protein tyrosine phosphatase (PTP) inhibitors, orthovanadate phenylarsine oxide, selectively block mGluR-LTD application group I mGluR agonist ( RS )-3,5-dihydroxyphenylglycine (DHPG-LTD), because NMDAR-LTD unaffected...
Two forms of NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) at hippocampal CA1 synapses can be distinguished based on their sensitivity to inhibitors protein kinase A (PKA). The PKA-dependent form requires multiple episodes high-frequency stimulation (HFS) or theta burst stimuli (TBS) with a spacing between in the order minutes. To investigate mechanism by which spaced induce LTP, we have compared, interleaved experiments, (s) and compressed (c) TBS protocols rat synapses. We...
Abstract Long-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or their single channel conductance (γ). Here, we have established how these distinct synaptic processes contribute to expression LTP slices obtained from young adult rodents. induced compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involves purely N (LTP ). In...
Abstract Astrocytes express a plethora of G protein-coupled receptors (GPCRs) that are crucial for shaping synaptic activity. Upon GPCR activation, astrocytes can respond with transient variations in intracellular Ca 2+ . In addition, -dependent and/or -independent release gliotransmitters occur, allowing them to engage bidirectional neuron-astrocyte communication. The development designer exclusively activated by drugs (DREADDs) has facilitated many new discoveries on the roles both...
Classically, long-term potentiation (LTP) at hippocampal CA1 synapses is triggered by the synaptic activation of NMDA receptors (NMDARs). More recently, it has been shown that calcium-permeable (CP)-AMPARs can also trigger plasticity these synapses. Specifically, their required for PKA and protein synthesis dependent component LTP typically induced delivery spaced trains high frequency stimulation. Here we present new data build upon ideas, including requirement low NMDAR dependence. We show...
Article30 April 2018Open Access Source DataTransparent process NMDAR-dependent Argonaute 2 phosphorylation regulates miRNA activity and dendritic spine plasticity Dipen Rajgor orcid.org/0000-0002-1855-9342 Centre for Synaptic Plasticity School of Biochemistry, University Bristol, UK Search more papers by this author Thomas M Sanderson Physiology, Pharmacology & Neuroscience, Mascia Amici Graham L Collingridge Department Faculty Medicine, Toronto, ON, Canada Lunenfeld-Tanenbaum Research...
The roles of Ca 2+ -induced calcium release in synaptic plasticity and metaplasticity are poorly understood. present study has addressed the role intracellular stores long-term potentiation (LTP) a form heterosynaptic known as tagging capture (STC) at CA1 synapses mouse hippocampal slices. effects two compounds, ryanodine cyclopiazonic acid (CPA), were examined on LTP induced by three distinct induction protocols: weak (w), compressed (c) spaced (s) theta-burst stimulation (TBS). These...
Abstract The removal of AMPA receptors from synapses is a major component long-term depression (LTD). How this occurs, however, still only partially understood. To investigate the trafficking in real-time we previously tagged GluA2 subunit with ecliptic pHluorin and studied effects NMDA receptor activation. In present study have compared effect group I mGluR activation, using super (SEP-GluA2) expressed cultured hippocampal neurons. Surprisingly, agonists two receptors, which are both able...
In area CA1 of the hippocampus, long-term depression (LTD) can be induced by activating group I metabotropic glutamate receptors (mGluRs), with selective agonist DHPG. There is evidence that mGluR-LTD expressed either a decrease in probability neurotransmitter release [P(r)] or change postsynaptic AMPA receptor number. However, what determines locus expression unknown. We investigated mechanisms using low (30 μM) high (100 concentration (RS)-DHPG. found 30 μM DHPG generated presynaptic LTD...
A major mechanism contributing to synaptic plasticity involves alterations in the number of AMPA receptors (AMPARs) expressed at synapses. Hippocampal CA1 synapses, where this process has been most extensively studied, are highly heterogeneous with respect their probability neurotransmitter release, P(r). It is unknown whether there any relationship between extent plasticity-related AMPAR trafficking and initial P(r) a synapse. To address question, we induced metabotropic glutamate receptor...
Long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission are forms plasticity that have been studied extensively thought to contribute learning memory. The reversal LTP, known as depotentiation (DP) has received far less attention however, its role in behavior is also from clear. Recently, deficits observed models schizophrenia, suggesting a greater understanding this form may help reveal the physiological alterations underlie symptoms experienced by patients....
Glycogen synthase kinase 3 (GSK-3) is a Ser/Thr protein that regulates many cellular processes, including synaptic plasticity. Previously, we reported inhibition of GSK-3 prevents the induction one major forms plasticity, N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD), in hippocampal slices. In present study, have investigated effects inhibiting on learning and memory healthy naïve animals. Systemic administration highly selective inhibitor, CT99021, reversibly...
Theta-burst stimulation (TBS) induces short-term potentiation (STP) plus two types of transcriptionally-independent forms long-term (LTP), termed LTP1 and LTP2. We have compared the susceptibility these three synaptic plasticity to depotentiation, induced by low frequency (LFS; 2 Hz for 10 min) at Schaffer collateral-commissural pathway in area CA1 adult rat hippocampal slices. In interleaved experiments, STP LTP were episodes either compressed or spaced TBS (cTBS sTBS). LFS had a more...
ABSTRACT Long-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or their single channel conductance (γ). Here we have established how these distinct synaptic processes contribute to expression LTP slices obtained from young adult rodents. induced compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involved purely N (LTP ). In contrast,...
Metaplasticity involves changes in the state of neurons or synapses that influence their ability to generate synaptic plasticity. One form heterosynaptic metaplasticity, known as tagging and capture (STC), has been intensively studied but underlying mechanisms are not fully understood. In experiments using hippocampal slices prepared from C57BL/6J mice, we have examined role group I metabotropic glutamate receptors (mGluRs) STC. We used a version STC where strong theta-burst stimulus (TBS),...