A5072895674- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Genetics and Neurodevelopmental Disorders
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Mitochondrial Function and Pathology
- Neurobiology and Insect Physiology Research
- Retinal Development and Disorders
- Neurogenesis and neuroplasticity mechanisms
- MicroRNA in disease regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Cytokine Signaling Pathways and Interactions
- Alzheimer's disease research and treatments
- Genetics, Aging, and Longevity in Model Organisms
- Neuroendocrine regulation and behavior
- Cholinesterase and Neurodegenerative Diseases
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- Amino Acid Enzymes and Metabolism
- Epilepsy research and treatment
University of Bristol
2010-2024
At Bristol
2013
University of California, Irvine
2005-2009
Istituto Pasteur
2005-2006
Fondazione Santa Lucia
2005
Sapienza University of Rome
2003
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is involved in many cellular processes, including cell growth differentiation, immune functions cancer. It activated by various cytokines, factors, protein tyrosine kinases (PTKs) regulates the genes. Of four JAK isoforms seven STAT known, JAK2 STAT3 are highly expressed brain where they present postsynaptic density (PSD). Here, we demonstrate a new neuronal function for JAK/STAT pathway. Using variety...
The mRNA levels of NKCC1, an inwardly directed Na + , K -2Cl − cotransporter that facilitates the accumulation intracellular Cl and KCC2, outwardly -Cl extrudes were studied in surgically resected brain specimens from drug-resistant temporal lobe (TL) epilepsy (TLE) patients. Quantitative RT-PCR analyses mRNAs extracted human TLE-associated regions revealed up-regulation NKCC1 a down-regulation KCC2 hippocampal subiculum, compared with hippocampus proper or TL neocortex, suggesting abnormal...
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...
Inhibition of Arp2/3-mediated actin polymerization by PICK1 is a central mechanism to AMPA receptor (AMPAR) internalization and long-term depression (LTD), although the signaling pathways that modulate this process in response NMDA (NMDAR) activation are unknown. Here, we define function for GTPase Arf1 process. We show Arf1-GTP binds limit PICK1-mediated inhibition Arp2/3 activity. Expression mutant does not bind leads reduced surface levels GluA2-containing AMPARs smaller spines...
Graphical Abstract figure legend HCN channels play an evolutionarily conserved pacemaker role in renal pelvic smooth muscle (RPSM) of lower and higher order mammals. The function hyperpolarization-activated cation (HCN) pacemakers remains controversial. Renal trigger contractions that expel waste from the kidney, have been localized to these tissues. To date, however, mechanisms underlying RPSM activity remain elusive. was investigated both (top left) (bottom mammalian models, which exhibit...
Synaptic plasticity is the process by which brain alters strength of its synaptic connections, a fundamental function that enables individuals to learn from experience. The study often involves application standard in vitro electrophysiological techniques hippocampal slice preparations. This unit discusses many special considerations are applicable for optimal this system. Most these principles also apply other
BackgroundThe discovery of coding variants in genes that confer risk intellectual disability (ID) is an important step toward understanding the pathophysiology this common developmental disability.MethodsHomozygosity mapping, whole-exome sequencing, and cosegregation analyses were used to identify gene responsible for syndromic ID with autistic features two independent consanguineous families from Arabian Peninsula. For vivo functional studies implicated gene's function cognition, Drosophila...
Pharmacotherapeutic strategies have been difficult to develop for several forms of temporal lobe epilepsy, which are consequently treated by surgical resection. To examine this problem, we studied the properties transmitter receptors tissues removed during treatment. We find that when cell membranes, isolated from neocortex patients afflicted with drug-resistant mesial epilepsy (TLE), injected into frog oocytes they acquire GABA type A (GABA -receptors) display a marked rundown repetitive...
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...
NMDA receptors (NMDARs) are ionotropic crucial for brain information processing. Yet, evidence also supports an ion-flux-independent signaling mode mediating synaptic long-term depression (LTD) and spine shrinkage. Here, we identify AETA (Aη), amyloid-β precursor protein (APP) cleavage product, as NMDAR modulator with the unique dual regulatory capacity to impact both modes. inhibits activity by competing co-agonist induces intracellular conformational modification of GluN1 subunits. This...
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...
It is currently unknown why glutamatergic presynaptic terminals express multiple types of glutamate receptors. We have addressed this question by studying both acute and long-term regulation mossy fibre function in the hippocampus. find that inhibition mGlu₁ mGlu₅ receptors together can block induction LTP. Furthermore, LTP be induced pharmacological activation either or receptors, provided kainate are also stimulated. Like conventional LTP, chemically-induced (chem-LTPm) depends on Ca²⁺...
Competitive N-methyl-d-aspartate receptor (NMDAR) antagonists bind to the GluN2 subunit, of which there are four types (GluN2A-D). We report that some N(1)-substituted derivatives cis-piperazine-2,3-dicarboxylic acid display improved relative affinity for GluN2C and GluN2D versus GluN2A GluN2B. These also subtype selectivity among more distantly related kainate family. Compounds 18i (-)-4 were most potent antagonists, was selective GluK1 GluK2, GluK3 AMPA receptors. Modeling studies revealed...
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...
Abstract Deregulation of GSK‐3β is strongly implicated in a variety serious brain conditions, such as Alzheimer disease, bipolar disorder and schizophrenia. To understand how becomes dysregulated these it important to its physiological functions the central nervous system. In this context, plays role induction NMDA receptor‐dependent long‐term depression (LTD) several substrates for have been identified form synaptic plasticity, including KLC‐2, PSD‐95 tau. Stabilization receptors at...
ABSTRACT Understanding the normal functions of GSK-3β in central nervous system is major interest because deregulation this kinase strongly implicated a variety serious brain conditions, such as Alzheimer disease, bipolar disorder and schizophrenia. plays role induction NMDA receptor-dependent long-term depression (LTD) several substrates for have been identified form synaptic plasticity, including KLC-2, PSD-95 tau. Stabilization receptors at synapses has also shown to involve GSK-3β, but...
NMDA receptors (NMDARs) are ionotropic crucial for brain information processing. Yet, evidence also supports an ion flux-independent signaling mode mediating synaptic long-term depression (LTD) and spine shrinkage. Here, we identify AETA (Aη), amyloid-b precursor protein (APP) cleavage product, as NMDAR modulator with the unique dual regulatory capacity to impact both modes. inhibits activity by competing co-agonist induces intracellular conformational modification of GluN1 subunits. This...