A5073271417- Olfactory and Sensory Function Studies
- Neurobiology and Insect Physiology Research
- Biochemical Analysis and Sensing Techniques
- Advanced Chemical Sensor Technologies
- Biochemical effects in animals
- Mast cells and histamine
- Nerve injury and regeneration
- Memory and Neural Mechanisms
- Insect Utilization and Effects
- Nuclear Structure and Function
- Urinary Bladder and Prostate Research
- Photochromic and Fluorescence Chemistry
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Consumer Attitudes and Food Labeling
- Biochemical and biochemical processes
- Insect and Arachnid Ecology and Behavior
- Receptor Mechanisms and Signaling
- Reproductive Biology and Fertility
- Sperm and Testicular Function
- Neuroendocrine regulation and behavior
Monell Chemical Senses Center
2013-2024
Philadelphia University
2021
Johns Hopkins University
2003-2010
Johns Hopkins Medicine
2004-2010
Forschungszentrum Jülich
2003
Howard Hughes Medical Institute
2003
University of Cambridge
1998-2001
Physiological Society
1998
For vertebrate olfactory signal transduction, a calcium-activated chloride conductance serves as major amplification step. However, the molecular identity of channel (CaCC) is unknown. Here we report proteomic screen for cilial membrane proteins mouse sensory neurons (OSNs) that identified all known transduction components well Anoctamin 2 (ANO2). Ano2 transcripts were expressed specifically in OSNs epithelium, and ANO2::EGFP fusion protein localized to OSN cilia when vivo using an...
Signaling by heterotrimeric GTP-binding proteins (G proteins) drives numerous cellular processes. The number of G protein molecules activated a single membrane receptor is determinant signal amplification, although in most cases this parameter remains unknown. In retinal rod photoreceptors, long-lived photoisomerized rhodopsin molecule activates many (transducins), yielding substantial amplification and large elementary (single-photon) response, before activity terminated. Here we report...
Odorants activate sensory transduction in olfactory receptor neurons (ORNs) via a cAMP-signaling cascade, which results the opening of nonselective, cyclic nucleotide–gated (CNG) channels. The consequent Ca2+ influx through CNG channels activates Cl channels, serve to amplify signal. We investigate here some general properties this Ca-activated channel rat, as well its functional interplay with channel, by using inside-out membrane patches excised from ORN dendritic knobs/cilia. At...
1 Response properties of isolated mouse olfactory receptor cells were investigated using the suction pipette technique. Cells exposed to odour cineole or solutions modified ionic content by rapidly changing solution superfusing cilia. All experiments performed at 37°C. 2 Mouse displayed a steep dependence action potential frequency on stimulus concentration, 3-fold increase in concentration often saturating firing 200-300 Hz. The current increased more gradually with increasing and did not...
The activation of G-protein-coupled olfactory receptors on the sensory neurons (OSNs) triggers a signaling cascade, which is mediated by heterotrimeric G-protein consisting α, β, and γ subunits. Although its α subunit, Gαolf, has been identified well characterized, identities β subunits their function in signal transduction, however, have not established yet. We, others, found expression Gγ13 epithelium, particularly cilia OSNs. In this study, we generated conditional gene knock-out mouse...
Olfactory receptor neurons (ORNs) in the nasal cavity detect and transduce odorants into action potentials to be conveyed olfactory bulb. Odorants are delivered ORNs via inhaled air at breathing frequencies that can vary from 2 10 Hz mouse. Thus transduction should occur sufficient speed such it accommodate repetitive frequent stimulation. Activation of odorant receptors (ORs) leads adenylyl cyclase III activation, cAMP increase, opening cyclic nucleotide-gated channels. This makes kinetic...
The Ca2+-activated Cl− channel TMEM16B is highly expressed in the cilia of olfactory sensory neurons (OSNs). Although a large portion odor-evoked transduction current carried by channels, their role olfaction still controversial. A previous report (Billig et al. 2011. Nat. Neurosci. http://dx.doi.org/10.1038/nn.2821) showed that disruption TMEM16b/Ano2 gene mice abolished currents OSNs but did not produce any major change behavior. Here we readdress and show knockout (KO) have behavioral...
To study the mechanism by which Ca2+, enters during odor response, is extruded response recovery, recordings were made from isolated frog olfactory receptor cells using suction pipette technique, while superfusing cilia with solutions of modified ionic composition. When external Na+ was substituted another cation, to greatly prolonged. This prolongation similar irrespective whether replaced Li+, permeates cyclic nucleotide-gated conductance, or choline, does not. The prolonged current...
Olfactory marker protein (OMP), a phylogenetically conserved protein, is highly, and almost exclusively, expressed in vertebrate olfactory receptor neurons (ORNs). Although OMP widely used as for ORNs, its function has remained largely elusive. Here we suction-pipette recordings from isolated ORNs of OMP(-/-) mice to investigate role transduction. Vertebrate transduction initiated when odourants bind proteins activate an adenylyl cyclase via G protein-coupled signalling pathway. This leads...
Mammalian odorant receptors form a large, diverse group of G protein–coupled that determine the sensitivity and response profile olfactory receptor neurons. But little is known if control basal also stimulus-induced cellular properties neurons other than ligand specificity. This study demonstrates different have varying degrees activity, which drives concomitant current fluctuations action potential firing. activity can be suppressed by odorants functioning as inverse agonists. Furthermore,...
Vertebrate olfactory receptor neurons (ORNs) are stimulated in a rhythmic manner vivo, driven by delivery of odorants to the nasal cavity carried inhaled air, making olfaction sense where animals can control frequency stimulus delivery. How ORNs encode repeated stimulation at resting, low breathing frequencies and increased sniffing is not known, nor it known if transduction cascade accurate fast enough follow high stimulation. We investigated mouse responses mimicking odorant exposure...
The sense of smell helps us navigate the environment, but its molecular architecture and underlying logic remain understudied. spatial location odorant receptor genes (Olfrs) in nose is thought to be independent structural diversity odorants they detect. Using transcriptomics, we create a genome-wide 3D atlas mouse olfactory mucosa (OM). Topographic maps differentially expressed space reveal that both Olfrs non-Olfrs are distributed continuous overlapping fashion over at least five broad...
1. Receptor current and spiking responses were recorded simultaneously from isolated frog olfactory receptor cells using the suction pipette technique. Cells stimulated with odour cineole by rapid exchange of solution bathing cilia. 2. The response to a 1 s stimulus increased in graded manner over 300-fold range concentration without clear saturation, was accompanied train action potentials. As increased, frequency firing also, until it saturated at highest concentrations. number spikes...
Olfactory receptor neurons (ORNs) employ a cyclic nucleotide-gated (CNG) channel to generate current in response an odorant-induced rise cAMP. This contains three types of subunits, the principal CNGA2 subunit and two modulatory subunits (CNGA4 CNGB1b). Here, we have analyzed functional relevance CNGB1 for olfaction by gene targeting mice. Electro-olfactogram responses CNGB1-deficient (CNGB1-/-) mice displayed reduced maximal amplitude decelerated onset recovery kinetics compared with...
An important contributing factor for the high sensitivity of sensory systems is exquisite receptor cells. We report here signaling threshold olfactory neuron (ORN). first obtained a best estimate size physiological electrical response successfully triggered by single odorant-binding event on frog ORN, which was ∼0.034 pA and had an associated transduction domain spanning only tiny fraction length ORN cilium. also estimated receptor-current to fire action potentials in odorant pulse, ∼1.2 pA....