A5043829212- Memory and Neural Mechanisms
- Neuroscience and Neuropharmacology Research
- Zebrafish Biomedical Research Applications
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Neuroendocrine regulation and behavior
- RNA Research and Splicing
- Fish Ecology and Management Studies
- Animal Behavior and Reproduction
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Stress Responses and Cortisol
- Neural dynamics and brain function
- Congenital heart defects research
- Cell Image Analysis Techniques
- Neonatal and fetal brain pathology
- Autism Spectrum Disorder Research
- Mass Spectrometry Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer, Hypoxia, and Metabolism
- Neurogenesis and neuroplasticity mechanisms
- Endoplasmic Reticulum Stress and Disease
- Child Development and Digital Technology
- Advanced Proteomics Techniques and Applications
Wayne State University
2020-2025
Hospital for Sick Children
2014-2021
Great Ormond Street Hospital
2021
University College London
2021
SickKids Foundation
2021
University of Southampton
2011-2017
Temple University
2007-2016
Temple College
2011
Social recognition memory is an essential and basic component of social behavior that used to discriminate familiar novel animals/humans. Previous studies have shown the importance several brain regions for memories; however, mechanisms underlying consolidation at molecular anatomic levels remain unknown. Here, we show a network necessary generation in mice. A mouse genetic study showed cAMP-responsive element-binding protein (CREB)-mediated transcription required formation memory....
BDNF signaling contributes to protein-synthesis-dependent synaptic plasticity, but the dynamics of TrkB and mechanisms translation have not been defined. Here, we show that long-term potentiation (LTP) consolidation in dentate gyrus live rodents requires sustained (hours) BDNF-TrkB signaling. Surprisingly, this activation maintains an otherwise labile pathway from MAP-kinase-interacting kinase (MNK). MNK activity promotes eIF4F initiation complex formation protein synthesis mechanistically...
Nicotine is known to enhance learning and memory in hippocampus-dependent tasks such as contextual fear conditioning. The present study was designed directly examine whether the hippocampus plays a role mediating this enhancement which nicotinic acetylcholine receptor (nAChR) subtypes localized are critical for enhanced learning. Contextual conditioning consisted of two white noise conditioned stimuli presentations, each coterminating with 2 s, 0.57 mA footshock separated by 120 s intertrial...
Growth arrest and DNA damage-inducible β ( Gadd45b ) has been shown to be involved in demethylation may important for cognitive processes. is abnormally expressed subjects with autism psychosis, two disorders associated deficits. Furthermore, several high-throughput screens have identified as a candidate plasticity-related gene. However, direct demonstration of link between memory not established. The current studies first determined whether expression the Gadd45 family genes was affected by...
Although the MAP kinase-interacting kinases (MNKs) have been known for >15 years, their roles in regulation of protein synthesis remained obscure. Here, we explore involvement MNKs brain-derived neurotrophic factor (BDNF)-stimulated cortical neurons from mice. Using a combination pharmacological and genetic approaches, show that BDNF-induced upregulation requires MEK/ERK signaling downstream kinase, MNK1, which phosphorylates eukaryotic initiation (eIF) 4E. Translation is mediated by...
Protein synthesis, especially translation elongation, requires large amounts of energy, which is often generated by oxidative metabolism. Elongation controlled phosphorylation eukaryotic elongation factor 2 (eEF2), inhibits its activity and catalyzed eEF2 kinase (eEF2K), a calcium/calmodulin-dependent α-kinase. Hypoxia causes the activation eEF2K induces independently previously known inputs into eEF2K. Here, we show that subject to hydroxylation on proline-98. Proline proline hydroxylases,...
Prosocial behavior, in particular helping others need, occurs preferentially response to distress of one’s own group members. In order explore the neural mechanisms promoting mammalian a discovery-based approach was used here identify brain-wide activity correlated with behavior rats. Demonstrating social selectivity, rats helped their strain (‘ingroup’), but not an unfamiliar (‘outgroup’), by releasing them from restrainer. Analysis via quantification early-immediate gene c-Fos identified...
Abstract Nicotine administration alters various forms of hippocampus‐dependent learning and memory. Increasing work has found that the dorsal ventral hippocampus differentially contribute to multiple behaviors. Thus, present study examined whether effects nicotine in have distinct influences on contextual fear male C57BL/6J mice. Direct infusion into resulted an enhancement learning, whereas infused deficits. infusions did not alter hippocampus‐independent cued conditioning or time spent...
Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation specific brain regions (systems level consolidation). However, the relationship between molecular and systems are poorly understood. Molecular mechanisms involved in initiation elongation have previously been studied cortex using taste-learning paradigms. For example, levels phosphorylation eukaryotic factor 2...
Zebrafish are a genetically tractable vertebrate that hold considerable promise for elucidating the molecular basis of behavior. Although numerous recent advances have been made in ability to precisely manipulate zebrafish genome, much less is known about many aspects learning and memory adult fish. Here, we describe development contextual fear conditioning paradigm using an electric shock as aversive stimulus. We find modulated by intensity, prevented established amnestic agent (MK-801),...
Individual differences in exploratory behavior have been found across a range of taxa and are thought to contribute evolutionary fitness. Animals that explore more novel environment visit areas high predation risk considered bold, whereas animals with the opposite behavioral pattern shy. Here, we determined whether this bimodal characterization bold versus shy adequately captures breadth variation zebrafish or if there than these two subtypes. To identify categories, applied unsupervised...
Modulation of the elongation phase protein synthesis is important for numerous physiological processes in both neurons and other cell types. Elongation primarily regulated via eukaryotic factor 2 kinase (eEF2K). However, consequence altering eEF2K activity on specific proteins largely unknown. Using pharmacological genetic manipulations combined with two protein-labeling techniques, stable isotope labeling amino acids culture bio-orthogonal non-canonical acid tagging, we identified a subset...
Zebrafish have gained prominence as a model organism in neuroscience over the past several decades, generating key insight into development and functioning of vertebrate brain. However, techniques for whole brain mapping adult stage zebrafish are lacking. Here, we describe pipeline built using open-source tools whole-brain activity zebrafish. Our combines advances histology, microscopy, machine learning to capture cfos across entirety Following tissue clearing, images captured light-sheet...
Eukaryotic elongation factor 2 kinase (eEF2K) negatively regulates the phase of mRNA translation and hence protein synthesis. Increasing evidence indicates that eEF2K plays an important role in survival migration cancer cells tumor progression. As demonstrated by two‐dimensional wound‐healing three‐dimensional transwell invasion assays, knocking down or inhibiting impairs cells. Conversely, exogenous expression eEF2 (the substrate eEF2K) accelerates wound healing invasion. Importantly, using...
The rapid regulation of cell signaling in response to calcium neurons is essential for real-time processing large amounts information the brain. A vital regulatory component, and one most energy-intensive biochemical processes cells, elongation phase mRNA translation, which controlled by Ca 2+ /CaM-dependent factor 2 kinase (eEF2K). However, little known about dynamics eEF2K despite its established role learning synaptic plasticity. To explore depth, we stimulated activity mouse primary...
Nicotine has been found to enhance learning in a variety of tasks, including contextual fear conditioning. During conditioning animals have learn the context and associate with an unconditioned stimulus (footshock). As both these types co-occur during conditioning, it is not clear whether nicotine enhances one or learning. To tease two forms apart, authors made use preexposure facilitation effect (CPFE). Acquisition CPFE requires that context-shock occurs on separate days, allowing for their...