A5023395524- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Ion channel regulation and function
- Neuroendocrine regulation and behavior
- Neuroscience of respiration and sleep
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Zebrafish Biomedical Research Applications
- Photoreceptor and optogenetics research
- RNA Research and Splicing
- Axon Guidance and Neuronal Signaling
- Pancreatic function and diabetes
- Genetic Syndromes and Imprinting
- Congenital heart defects research
- Insect and Pesticide Research
- Pluripotent Stem Cells Research
- Heart Rate Variability and Autonomic Control
- Neurobiology and Insect Physiology Research
- Stress Responses and Cortisol
- Single-cell and spatial transcriptomics
- Circadian rhythm and melatonin
- 14-3-3 protein interactions
- Neuropeptides and Animal Physiology
Case Western Reserve University
2013-2025
University School
1995-2021
Neurosciences Institute
2005-2012
Western University of Health Sciences
2006
Target (United States)
2005
Salk Institute for Biological Studies
1987-1991
Baylor College of Medicine
1991
Ipsen (France)
1991
Howard Hughes Medical Institute
1988
University of California, Los Angeles
1984-1985
Abstract Previous studies have revealed the existence of a gene family that encodes group neuronal nicotinic acetylcholine receptor (nAChR) subunits. Four members this been characterized thus far; three these subunits (alpha2, alpha3, and alpha4) are structurally related to ligand binding subunit expressed in muscle form functional nAChRs when combined with beta2 product Xenopus oocytes. In addition, alpha4 appears encode two different products (alpha4‐1 alpha4‐2) proposed arise by...
Three closely related genes, GluR1, GluR2, and GluR3, encode receptor subunits for the excitatory neurotransmitter glutamate. The proteins encoded by individual genes form homomeric ion channels in Xenopus oocytes that are sensitive to glutamatergic agonists such as kainate quisqualate but not N -methyl-D-aspartate, indicating binding sites exist on single polypeptides. In addition, kainate-evoked conductances potentiated expressing two or more of cloned subunits. Electrophysiological...
A family of genes coding for proteins homologous to the alpha subunit muscle nicotinic acetylcholine receptor has been identified in rat genome. These are transcribed central and peripheral nervous systems areas known contain functional receptors. In this paper, we demonstrate that three these genes, which call 3, 4, beta 2, encode form receptors when expressed Xenopus oocytes. Oocytes expressing either 3 or 4 protein combination with 2 produced a strong response acetylcholine. only gave...
Serotonergic neurons project widely throughout the CNS and modulate many different brain functions. Particularly important, but controversial, are contributions of serotonin (5-HT) to respiratory thermoregulatory control. To better define roles 5-HT in breathing thermoregulation, we took advantage a unique conditional knock-out mouse which Lmx1b is genetically deleted Pet1 -expressing cells ( f/f/p ), resulting near-complete absence central neurons. Here, show that hypercapnic ventilatory...
A new type of agonist-binding subunit rat neuronal nicotinic acetylcholine receptors (nAChRs) was identified. Rat genomic DNA and complementary encoding this (alpha2) were cloned analyzed. Complementary expression studies in Xenopus oocytes revealed that the injection messenger RNAs (mRNAs) for alpha2 beta2 (a nAChR subunit) led to generation a functional nAChR. In contrast other known nAChRs, receptor produced by mRNAs resistant α-neurotoxin Bgt3.1. situ hybridization histochemistry showed...
We have identified two additional members of the neuronal nicotinic acetylcholine receptor (nAChR)-related gene family. cDNA clones for one new gene, designated alpha 5, were isolated from rat hippocampus and PC12 cell line libraries. The 5 encodes a protein 48,800 daltons (424 amino acids) which exhibits significant overall acid sequence identity with previously cloned nAChR subunits 1 (49%), 2 (55%), 3 (52%), 4 (49%). Features characteristic other alpha-subunits are present such as...
Serotonin (5-HT) plays a crucial neuromodulatory role in numerous physiological and behavioral functions, dysfunction of the serotonergic system has been implicated several psychiatric disorders. Despite widespread importance central neurotransmitter system, little is known about molecular mechanisms controlling development 5-HT neurons. We previously identified an ETS domain transcription factor, Pet-1, that expressed small number tissues, including brain. Here, we show expression Pet-1 RNA...
Abstract Screening of a rat brain cDNA library with radiolabeled probe made from an alpha 3 (Boulter, J., Evans, K., Goldman, D., Martin, G., Treco, Heinemanns, S., and Patrick, J. (1986) Nature 319, 368-374) resulted in the isolation clone whose sequence encodes protein, beta 3, which is homologous (40-55% amino acid identity) to previously described neuronal nicotinic acetylcholine receptor subunits. The encoded protein has structural features found other (nAChR) Two cysteine residues that...
Serotonin (5HT) is a critical modulator of neural circuits that support diverse behaviors and physiological processes, multiple lines evidence implicate abnormal serotonergic signaling in psychiatric pathogenesis. The significance 5HT underscores the importance elucidating molecular pathways involved system development, function, plasticity. However, these mechanisms remain poorly defined, owing largely to difficulty accessing neurons for experimental manipulation. To address this...
Central serotonergic neurons have been implicated in numerous animal behaviors and psychiatric disorders, but the molecular mechanisms underlying their development are not well understood. Here we generated Lmx1b (LIM homeobox transcription factor 1 β) conditional knock-out mice ( f/f/p ) which was only deleted Pet1 (pheochromocytoma 12 ETS factor-1)-expressing 5-HT neurons. In mice, initial generation of central appeared normal. However, expression both 5-HT-specific non-5-HT-specific...
Growing evidence supports a major contribution of cortical serotonin (5-hydroxytryptamine, 5-HT) to the modulation cognitive flexibility and inflexibility evident in neuropsychiatric disorders. The precise role 5-HT influence gene variation mediating this process is not fully understood. Using touch screen–based operant system, we assessed reversal pairwise visual discrimination as an assay for flexibility. Effects constitutive genetic or pharmacological inactivation transporter (5-HTT) on...
Respiratory motoneuron response to hypoxia is reflex in nature and carotid body sensory receptor constitutes the afferent limb of this reflex. Recent studies showed that repetitive exposures evokes long term facilitation nerve discharge (sLTF) rodents exposed chronic intermittent (CIH). Although with anti-oxidants suggested involvement reactive oxygen species (ROS)-mediated signaling eliciting sLTF, source mechanisms associated ROS generation have not yet been investigated. We tested...