A5036722576- Parkinson's Disease Mechanisms and Treatments
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
- Neurological disorders and treatments
- Photoreceptor and optogenetics research
- Conducting polymers and applications
- Neonatal and fetal brain pathology
- Nicotinic Acetylcholine Receptors Study
- Neuroscience of respiration and sleep
- Neuroscience and Neural Engineering
- Receptor Mechanisms and Signaling
- Alzheimer's disease research and treatments
- Neuroendocrine regulation and behavior
Marine Biological Laboratory
2020-2023
University of Pittsburgh
2023
Yale University
2014-2023
Institute of Biophysics and Biomedical Engineering
2010
Institute of Biomedical Science
2010
Austral University of Chile
2008-2010
University of Chile
2008-2009
Genetic and pathological studies link α-synuclein to the etiology of Parkinson9s disease (PD), but normal function this presynaptic protein remains unknown. α-Synuclein, an acidic lipid binding protein, shares high sequence identity with β- γ-synuclein. Previous have implicated synucleins in synaptic vesicle (SV) trafficking, although precise site synuclein action continues be unclear. Here we show, using optical imaging, electron microscopy, slice electrophysiology, that are required for...
Synucleins (α, β, γ-synuclein) are a family of abundant presynaptic proteins. α-Synuclein is causally linked to the pathogenesis Parkinson's disease (PD). In an effort define their physiological and pathological function or functions, we investigated effects deleting synucleins overexpressing α-synuclein PD mutations, in mice, on synapse architecture using electron microscopy (EM) cryoelectron tomography (cryo-ET). We show that regulators presynapse size synaptic vesicle (SV) pool...
Slow and persistent synaptic inhibition is mediated by metabotropic GABA B receptors (GABA Rs). Rs are responsible for the modulation of neurotransmitter release from presynaptic terminals hyperpolarization at postsynaptic sites. Postsynaptic predominantly found on dendritic spines, adjacent to excitatory synapses, but control their plasma membrane availability still controversial. Here, we explore role glutamate receptor activation in regulating function surface central neurons. We...
The discovery of synaptic nanostructures revealed key insights into the molecular logic function and plasticity. Yet, our understanding how diverse synapses in brain organize their nano-architecture remains elusive, largely due to limitations super-resolution imaging complex tissue. Here, we characterized single-domain camelid nanobodies for 3D quantitative multiplex nano-organization sing tau-STED nanoscopy cryosections from mouse primary somatosensory cortex. We focused on thalamocortical...
α-Synuclein is a presynaptic protein that regulates synaptic vesicle (SV) trafficking. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), α-synuclein aberrantly accumulates throughout neurons, including at synapses. During neuronal activity, reversibly phosphorylated serine 129 (pS129). While pS129 comprises ∼4% of total under physiological conditions, it dramatically increases in PD DLB brains. The impacts excess on function are currently unknown. We show here compared...
The efficacy of synaptic transmission depends on the availability ionotropic and metabotropic neurotransmitter receptors at plasma membrane, but contribution endocytic recycling pathways in regulation gamma-aminobutyric acid type B (GABA(B)) remains controversial. To understand mechanisms that regulate abundance GABA(B) receptors, we have studied their turnover combining surface biotin labeling a microscopic immunoendocytosis assay hippocampal cortical neurons. We report internalization is...
Synucleinopathies are neurological disorders associated with α-synuclein overexpression and aggregation. While it is well established that of wild type (α-syn-140) leads to cellular toxicity neurodegeneration, much less known about other naturally occurring splice isoforms. In this study we provide the first detailed examination synaptic effects caused by one these isoforms, α-synuclein-112 (α-syn-112). α-Syn-112 produced an in-frame excision exon 5, resulting in deletion amino acids 103-130...
α-Synuclein and family members β- γ-synuclein are presynaptic proteins that sense generate membrane curvature, properties important for synaptic vesicle (SV) cycling. αβγ-synuclein triple knockout neurons exhibit SV endocytosis deficits. Here, we investigated if α-synuclein affects clathrin assembly in vitro. Visualizing on membranes using a lipid monolayer system revealed increases lattices size curvature. On cell membranes, observe is colocalized with its adapter AP180 concentric ring...
Abstract α-Synuclein and family members β-, γ-synuclein, are presynaptic proteins that sense generate membrane curvature, properties important for synaptic vesicle (SV) cycling. αβγ-synuclein triple knockout (KO) neurons exhibit SV endocytosis (SVE) deficits. Here, we investigate how SVE is regulated by α-synuclein. Immuno-electron microscopy (EM) of synaptosomes reveals α-synuclein relocalizes from SVs to the upon stimulation, allowing function on membranes during or after stimulation. On...
ABSTRACT Synucleinopathies are neurological disorders associated with α-synuclein overexpression and aggregation. While it is well established that of wild type (α-syn-140) leads to cellular toxicity neurodegeneration, much less known about other naturally occurring splice isoforms. In this study we provide the first detailed examination synaptic effects caused by one these isoforms, α-synuclein-112 (α-syn-112). α-Syn-112 produced an in-frame excision exon 5, resulting in deletion amino...