A5023714956- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Retinal Diseases and Treatments
- Ion Channels and Receptors
- Neuroscience and Neural Engineering
- Receptor Mechanisms and Signaling
- Neurobiology and Insect Physiology Research
- Amino Acid Enzymes and Metabolism
- Lipid Membrane Structure and Behavior
- melanin and skin pigmentation
- Ion channel regulation and function
- Circadian rhythm and melatonin
- Calcium signaling and nucleotide metabolism
- Connexins and lens biology
- Cardiac electrophysiology and arrhythmias
- Neuroinflammation and Neurodegeneration Mechanisms
- Pancreatic function and diabetes
- Glaucoma and retinal disorders
- Autoimmune Neurological Disorders and Treatments
- Nicotinic Acetylcholine Receptors Study
- Anesthesia and Neurotoxicity Research
- Barrier Structure and Function Studies
- Ocular Diseases and Behçet’s Syndrome
Oregon Health & Science University
2016-2025
Imperial College Healthcare NHS Trust
2023
Oregon Medical Research Center
2016
St Thomas' Hospital
2015
University of Portland
2013
American Society of Safety Professionals
2010
Australian National University
2001-2002
Neuroscience Research Australia
1998-2001
Max Planck Society
1996-2000
ACT Government
2000
The ON pathway of the visual system, which detects increases in light intensity, is established at first retinal synapse between photoreceptors and ON-bipolar cells. Photoreceptors hyperpolarize response to reduce rate glutamate release, turn causes depolarization This cell mediated by metabotropic receptor, mGluR6, controls activity a depolarizing current. Despite intensive research over past two decades, molecular identity channel that generates this current has remained elusive. Here, we...
Glutamate release from photoreceptor terminals is controlled by voltage-dependent calcium channels (VDCCs). In humans, mutations in the Cacna1f gene, encoding α 1F subunit of VDCCs, underlie incomplete form X-linked congenital stationary night blindness (CSNB2). These impair synaptic transmission rod and cone photoreceptors to bipolar cells. Here, we report anatomical functional characterizations retina nob2 ( no b-wave 2 ) mouse, a naturally occurring mutant caused null mutation . Not...
Ribbon synapses of vertebrate photoreceptors constantly release glutamate in darkness. Transmitter is maintained by a steady influx calcium through voltage-dependent channels, implying the presence mechanism that able to extrude at an equal rate. The two predominant mechanisms intracellular extrusion are plasma membrane ATPase (PMCA) and Na + /Ca 2+ -exchanger. Immunohistochemical staining retina sections revealed strong immunoreactivity for PMCA rod cone terminals, whereas -exchanger was...
In contrast to conventional synapses, which release neurotransmitter transiently, ribbon synapses formed by photoreceptors and bipolar cells of the retina continuously modulate rate in response light. Both modes are mediated synaptic vesicles but probably differ regulation docking fusion with plasma membrane. We have found that syntaxin 1, an essential component core complex is absent from retina, raising possibility these contain a different type or syntaxin-like protein. By...
The genetic locus for incomplete congenital stationary night blindness (CSNB2) has been identified as the CACNA1f gene, encoding α 1F calcium channel subunit, a member of L-type family channels. electroretinogram associated with CSNB2 implicates in synaptic transmission between retinal photoreceptors and bipolar cells. Using recently developed monoclonal antibody to , we localize ribbon active zones rod photoreceptor terminals mouse retina, supporting role mediating glutamate release from...
For almost 30 years the ion channel that initiates ON visual pathway in vertebrate vision has remained elusive. Recent findings now indicate pathway, which begins with unbinding of glutamate from metabotropic receptor 6 (mGluR6), ends opening transient potential (TRP)M1 cation channel. As a component mGluR6 signal transduction mutations TRPM1 would be expected to cause congenital stationary night blindness (CSNB), and several such have already been identified CSNB families. Furthermore,...
In spiking neurons, phasic, calcium-dependent transmitter release is initiated when a presynaptic action potential activates voltage-dependent calcium channels. Vertebrate photoreceptors are nonspiking neurons that continuously transmitter. This study uses patch-clamp recording to examine the electrophysiological properties of mammalian cones in intact retina. The cell capacitance was 10 ± 1 pF and input resistance 0.52 0.46 G-ohms at −65 mV (31 cells). A specific membrane 1.2 pF/cm2...
Abstract Mutations in LRIT 3 lead to complete congenital stationary night blindness ( cCSNB ). The exact role of ON ‐bipolar cell signaling cascade remains be elucidated. Recently, we have characterized a novel mouse model lacking Lrit3 [ no b‐wave 6, nob6 / )], which displays similar abnormalities patients with mutations. Here compare the localization components wild‐type and retinal sections by immunofluorescence confocal microscopy. An anti‐ antibody was generated. Immunofluorescent...
Purpose Photophobia is a common and debilitating symptom associated with migraine. Women are disproportionately affected by migraines, higher prevalence more severe symptoms compared to men. This study investigated the effects of cortical spreading depression on light-aversive dark-seeking behaviors in rat model, an emphasis sex differences. Method Experiments were conducted seven eight-week-old male female Sprague Dawley rats. was modeled injections potassium chloride or artificial...
Synaptophysin and synaptoporin are homologous proteins that among the most abundant synaptic vesicle proteins. Despite their high degree of sequence similarity, they differentially distributed in brain. The distribution synaptophysin was examined adult rat rabbit retina by using single- double-labeling immunocytochemistry with conventional light microscopy confocal laser scanning microscopy. In retina, immunoreactivity found outer plexiform layer terminals photoreceptors homogeneously...
Plasma membrane anion exchangers constitute a multigene family that contributes to the regulation of intracellular pH and chloride concentration in many cell types. We have characterized two polypeptide isoforms AE3 gene are expressed rat retina. Using antipeptide antibodies specific for defined NH2-terminal COOH-terminal epitopes, we identified 165 kDa whose expression is restricted primary glial type retina, Müller cell, 125 horizontal neurons. Expression isoform exhibits polarized...
Abstract Bipolar cells convey information through the retina via graded changes in their membrane potential and modulate transmitter release influx of calcium L‐type channels. However, molecular identity α 1 subunit has not been confirmed. We report presence newly cloned 1F mouse bipolar cell synaptic terminals. The subunits are localized to hot spots, possibly corresponding active zones. also physiological properties two currents present cells, a low‐voltage‐activated current T‐type...
Abstract The nob2 mouse carries a null mutation in the Cacna1f gene, which encodes pore‐forming subunit of L‐type calcium channel, Ca v 1.4. loss electroretinogram b‐wave these mice suggests severe reduction transmission between photoreceptors and second‐order neurons retina supports central role for 1.4 channel at photoreceptor ribbon synapses, to it has been localized. Here we show that leads aberrant outgrowth rod bipolar cell dendrites horizontal processes into outer nuclear layer (ONL)...
Abstract Complete X‐linked congenital stationary night blindness (CSNB1) is a hereditary visual disease characterized by abnormalities in both the dark‐ and light‐adapted electroretinogram, consistent with defect synaptic transmission between photoreceptors ON‐bipolar cells. The gene responsible for CSNB1, NYX , encodes novel, leucine‐rich repeat protein, nyctalopin. Consistent its predicted glycosylphosphatidylinositol linkage, we show that recombinant nyctalopin targeted to extracellular...
We performed genome-wide chemical mutagenesis of C57BL/6J mice using N -ethyl- -nitrosourea (ENU). Electroretinographic screening the third generation offspring revealed two G3 individuals from one G1 family with a normal a-wave but lacking b-wave that we named nob4 . The mutation was transmitted recessive mode inheritance and mapped to chromosome 11 in region containing Grm6 gene, which encodes metabotropic glutamate receptor protein, mGluR6. Sequencing confirmed single nucleotide...
Horizontal cells mediate inhibitory feedforward and feedback lateral interactions in the outer retina at photoreceptor terminals bipolar cell dendrites; however, mechanisms that underlie synaptic transmission from mammalian horizontal are poorly understood. The localization of a vesicular γ-aminobutyric acid (GABA) transporter (VGAT) to processes primate rodent retinae suggested release transmitter manner. Toward determining whether molecular machinery for is present cells, we investigated...
Electrical coupling, mediated by gap junctions, contributes to signal averaging, synchronization, and noise reduction in neuronal circuits. In addition, junctions may also provide alternative pathways. However, because they are small especially difficult image, often ignored large-scale 3D reconstructions. Here, we reconstruct between photoreceptors the mouse retina using serial blockface-scanning electron microscopy, focused ion beam-scanning confocal microscopy for junction protein Cx36....