A5004294961- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Genetics and Neurodevelopmental Disorders
- Photoreceptor and optogenetics research
- Neurogenesis and neuroplasticity mechanisms
- Memory and Neural Mechanisms
- Autism Spectrum Disorder Research
- Neural dynamics and brain function
- Neurotransmitter Receptor Influence on Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neural Engineering
- Axon Guidance and Neuronal Signaling
- Alzheimer's disease research and treatments
- Epilepsy research and treatment
- Functional Brain Connectivity Studies
- Ubiquitin and proteasome pathways
- Phosphodiesterase function and regulation
- Cellular transport and secretion
- Cholinesterase and Neurodegenerative Diseases
- Photochromic and Fluorescence Chemistry
- RNA regulation and disease
- RNA Interference and Gene Delivery
- RNA Research and Splicing
Northwestern University
2015-2024
Northwestern University
2019-2023
Czech Academy of Sciences, Institute of Physiology
2015
New York Oncology Hematology
2011
Centre Hospitalier Universitaire de Saint-Étienne
2011
Saratoga Hospital
2011
Johns Hopkins Medicine
2009
Johns Hopkins University
2009
University of Rochester
2009
Salk Institute for Biological Studies
1998-2004
To report the metabotropic glutamate receptor 5 (mGluR5) as autoantigen of antibodies from 2 patients with Hodgkin lymphoma (HL) and limbic encephalopathy (Ophelia syndrome).Immunohistochemistry brain tissue cultures rat hippocampal neurons were used to demonstrate antibodies. Immunoprecipitation, mass spectrometry, mGluR5-null mice served identify antigen. HEK293 cells transfected mGluR5 or mGluR1 determine immunologic crossreactivity.Both developed symptoms consistent encephalopathy; one...
Delays in synaptic and neuronal development the cortex are key hallmarks of fragile X syndrome, a prevalent neurodevelopmental disorder that causes intellectual disability sensory deficits is most common known cause autism. Previous studies have demonstrated normal progression plasticity refinement during critical period altered mice. Although disruptions excitatory synapses well documented X, there less about inhibitory neurotransmission period. GABAergic transmission plays crucial trophic...
Abstract The etiology of major depressive disorder (MDD), the leading cause worldwide disability, is unknown. neurogenic hypothesis proposes that MDD linked to impairments adult neurogenesis in hippocampal dentate gyrus (DG), while effects antidepressants are mediated by increased neurogenesis. However, alterations and endophenotypes not always causally linked, relationship between altered behavior controversial. To address causality, we used chemogenetics transgenic mice selectively...
Functional NMDA receptors are heteromultimeric complexes of the NR1 subunit in combination with at least one four NR2 subunits (A-D). Coexpression NR3A, an additional receptor family, modifies NMDA-mediated responses. It is unclear whether NR3A interacts directly and/or and how such association might regulate intracellular trafficking membrane expression NR3A. Here we show that coassembles NR1-1a NR2A to form a complex distinct single-channel properties reduced relative calcium permeability....
The site of induction long-term potentiation (LTP) at mossy fiber–CA3 synapses in the hippocampus is unresolved, with data supporting both pre- and postsynaptic mechanisms. Here we report that fiber LTP was reduced by perfusion neurons peptides antibodies interfere binding EphB receptor tyrosine kinases (EphRs) to PDZ protein GRIP. Mossy also extracellular application soluble forms B-ephrins, which are normally membrane-anchored presynaptic ligands for receptors. ephrins increased basal...
Kainate receptors (KARs) play an important role in synaptic physiology, plasticity, and pathological phenomena such as epilepsy. However, the physiological implications for neuronal networks of distinct expression patterns KAR subunits are unknown. Using knock-out mice, we show that glutamate receptor (GluR) 5 GluR6 roles kainate-induced gamma oscillations epileptiform burst activity. Ablation GluR5 leads to a higher susceptibility network oscillogenic epileptogenic effects kainate, whereas...
The mechanisms that contribute to the extinction of previously acquired memories are not well understood. These processes, often referred as inhibitory learning, thought be parallel learning require a reacquisition new information and suppression experiences in order adapt novel situations. Using newly generated metabotropic glutamate receptor 5 (mGluR5) knock-out mice, we investigated role mGluR5 acquisition reversal an associative conditioned task spatial reference task. We found fear...
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disabilities and a leading autism. FXS caused by trinucleotide expansion in gene FMR1 on chromosome. The neuroanatomical hallmark an overabundance immature dendritic spines, factor thought to underlie synaptic dysfunction impaired cognition. We showed that aberrantly increased activity Rho GTPase Rac1 inhibited actin-depolymerizing cofilin, major determinant spine structure, disease-associated abnormalities...
Conditional loss of BACE1 in adult mouse brain results abnormalities the hippocampal mossy fiber pathway, which is important for learning and memory.
Highlights•The loss of BIN1 in neurons leads to impaired spatial memory consolidation•Neuronal Bin1 cKO mice have deficits excitatory synaptic transmission•BIN1 regulates presynaptic vesicular release hippocampal synapses•The results highlight a non-redundant role for regulationSummaryBIN1, member the BAR adaptor protein family, is significant late-onset Alzheimer disease risk factor. Here, we investigate function brain using conditional knockout (cKO) models. Loss neuronal expression select...
To understand the physiological role of kainate receptors and their participation in seizure induction animal models epilepsy, it will be necessary to develop a comprehensive description action CA3 region hippocampus. Activation presynaptic depresses excitatory synaptic transmission at mossy fiber associational-commissural inputs pyramidal neurons (Vignes et al., 1998; Bortolotto 1999; Kamiya Ozawa, 2000). In this study, we use gene-targeted mice lacking glutamate receptor 5 (GluR5) or GluR6...
Multimeric assemblies of kainate (KA) receptor subunits form glutamate-gated ion channels that mediate EPSCs and function as presynaptic modulators neurotransmitter release at some central synapses. The KA2 subunit is a likely constituent many neuronal receptors, because it widely expressed in most neurons the CNS. We have studied effect genetic ablation this on synaptic transmission mossy-fiber–CA3 pyramidal cell synapse hippocampal slices, where receptors are localized to both postsynaptic...
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and results from loss fragile mental retardation protein (FMRP). Many X-related cognitive behavioral features emerge during childhood are associated with abnormal synaptic cellular organization cerebral cortex. Identifying roles FMRP in cortical development will provide a basis for understanding pathogenesis syndrome. However, how influences developmental trajectory maturation remains unclear. We took...
Presynaptic terminal cAMP elevation plays a central role in plasticity at the mossy fiber-CA3 synapse of hippocampus. Prior studies have identified protein kinase A as downstream effector that contributes to fiber LTP (MF-LTP), but potential contribution Epac2, another expressed MF synapse, has not been considered. We investigated Epac2 MF-CA3 neurotransmission using −/− mice. The deletion did cause gross alterations hippocampal neuroanatomy or basal synaptic transmission. Synaptic...
Compromised protein homeostasis underlies accumulation of plaques and tangles in Alzheimer's disease (AD). To observe turnover at early stages amyloid beta (Aβ) proteotoxicity, we performed pulse-chase proteomics on mouse brains three genetic models AD that knock alleles precursor (APP) prior to the during progression. At initial Aβ accumulation, proteins associated with presynaptic terminals is selectively impaired. Presynaptic impaired turnover, particularly synaptic vesicle...