Abstracts - Association for Chemoreception Sciences

This interplay could be mediated by neuroendocrine signals like
insulin and/or leptin as their receptors have been described at
peripheral (olfactory epithelium) and central (olfactory bulb, OB)
levels. To test this hypothesis, we studied the modulation of the
activity of the olfactory sensory neurons (OSN) by hormonal
peptides. Using patch-clamp recordings in an in vitro intact
epithelium, we showed that insulin- or leptin-perfusion
significantly raises the spontaneous firing frequency of the OSN.
Moreover, these hormones decrease the OSN transduction
current and receptor potential recorded during odorant
stimulation. Therefore by increasing the spontaneous activity but
reducing the odorant-induced activity of OSN, an elevated insulin
and leptin level may result in a decreased global signal to-noise
ratio in the olfactory epithelium. This input to the bulb is further
modulated by the main output neurons of the OB (mitral cells,
MC). The MC are one of the central targets of these hormones:
MC express insulin receptors and their discharge is modulated by
insulin or leptin. This effect would underlie our behavioral tests
where an icv injection of either insulin or leptin decreases
olfactory detection. Thus insulin and leptin act in the olfactory
system both at peripheral and OB levels to modulate olfactory
sensitivity. The role of olfaction in the control of food intake
appears crucial and needs to be investigated further in order to
better understand alimentary pathologies. Acknowledgements:
This grant was supported by the Agence Nationale de la
Recherche (ANR), the French national research agency (project
ANR-05-PNRA-1.E7 AROMALIM)
#37 SYMPOSIUM - CHEMORECEPTION
IN CONTEXT: INTERACTIONS WITH
ENDOCRINE SYSTEMS AND METABOLIC STATE
The olfactory bulb as a metabolic sensor via insulin modulation
Debra A. Fadool 1,2 , Kristal Tucker 2 , David R. Marks 2 , Melissa A.
Cavallin 2 , James M. Overton 3 , Paola Pedarzani 4
1
Florida State University Program in Neuroscience and Molecular
Biophysics Tallahassee, FL, USA, 2 Florida State University
Department of Biological Sciences Tallahassee, FL, USA, 3 Florida
State University Department of Biomedical Sciences and Program
in Neuroscience Tallahassee, FL, USA, 4 Research Department of
Neuroscience, Physiology and Pharmacology, University College
London London, United Kingdom
Gene-targeted deletion of a predominant voltage-dependent
potassium channel, Kv1.3, in mitral cells of the olfactory bulb
results in a gamut of phenotypic changes including a “supersmeller”
ability, supernumerary axonal projections to
heterogenous glomeruli, and an alternation in action potential
discharge frequency. Kv1.3 is a substrate for tyrosine
phosphorylation and the molecular targets for modulation by the
hormone insulin have been mapped along the N- and C-termini
of the channel. Our laboratory has developed awake, intranasal
insulin delivery approaches that demonstrate a robust
phosphorylation of the channel that is linked to the behavioral but
not anatomical modifications of the knockout model. Recently
the laboratory has discovered that the channel is also responsible
for regulating body weight and that both diet- and geneticallyinduced
obesity can be abrogated via gene-targeted deletion of the
channel, or uniquely by olfactory bulbectomy that manipulates
total energy expenditure. We have now recorded on acute and
chronic insulin treated mice as well as diet-induced obese mice
and will present an electrophysiological analysis performed on
brain slices of how metabolic state alters neuronal responses in
mitral cells of the olfactory bulb. High fat diet has additionally
demonstrated an anatomical loss of olfactory sensory neurons,
presynaptic to the mitral cell input. Acknowledgements: This
work was supported by NIH DC03387 and NIH DC00044 from
the NIDCD and sabbatical award from FSU.
#38 SYMPOSIUM - CHEMORECEPTION
IN CONTEXT: INTERACTIONS WITH
ENDOCRINE SYSTEMS AND METABOLIC STATE
Roles of taste signaling molecules in endocrine cells in pancreas
and tongue
Zaza Kokrashvili, Peihua Jiang, Bedrich Mosinger, Robert F.
Margolskee
Monell Chemical Senses Center Philadelphia, PA, USA
Ga-gustducin, T1r receptors and other taste signaling elements
are expressed in duodenal enteroendocrine L cells that express
insulinotropic glucagon-like peptide 1 (GLP-1). Gustducin and
T1r3, well known for their roles in taste signaling, are essential for
L cell release of GLP-1 in response to glucose. We examined taste
cells to determine if they too expressed hormones typical of
intestinal enteroendocrine cells. Taste cells were found to express
GLP-1, glucagon, PYY and other gut hormones. Patterns of
expression indicated that gustducin-expressing type II taste cells
and other subtypes of taste cells express GLP-1. We also examined
the function of hormones released from these “endocrine taste
cells”. In wild-type mice, with or without esophagealectomy/
vagotomy, application of glucose to the tongue induced a rapid
elevation of GLP-1 in the bloodstream. Stimulation of taste cell
explants from wild-type mice with glucose led to release of
GLP-1 into the medium. Stimulation of gustducin-null mice with
glucose did not lead to significant release of GLP-1 from taste
cells in vivo or in explants. At least a portion of the cephalic phase
rise in circulating GLP-1 depends on direct release of GLP-1 from
taste cells into the bloodstream and requires gustducin. Taste
receptors, Ga-gustducin and downstream proteins were also
found to be expressed in several types of pancreatic islet cells.
Ga-gustducin is expressed in alpha cells, and T1R3 is expressed
in alpha and beta cells. Functional assays showed that in wild
type mice, but not in T1R3 null mice, T1R3 receptors mediate
increased secretion of insulin in response to artificial sweeteners
and sweet tasting amino-acids. Acknowledgements: Supported by
NIH grants DC03055 and DC03155 to RFM
#39 SYMPOSIUM - CHEMORECEPTION
IN CONTEXT: INTERACTIONS WITH
ENDOCRINE SYSTEMS AND METABOLIC STATE
Mechanisms of alimentary chemosensation and modulation
C. Shawn Dotson 1 , Amanda E.T. Elson 2 , Steven D. Munger 2
1
Department of Neuroscience & Center for Smell and Taste,
University of Florida College of Medicine Gainesville, FL, USA,
2
Department of Anatomy & Neurobiology, University of
Maryland School of Medicine Baltimore, MD, USA
Chemosensory cells throughout the alimentary canal use a
common molecular toolkit to detect and respond to nutrients and
other chemostimuli. For example, “taste” transduction molecules
(e.g., TAS1R and TAS2R receptors, gustducin) regulate hormonal
secretion in the gut. We have reported that a loss-of-function
variant of a human TAS2R is associated with glucose
dysregulation and the presence of Type 2 diabetes mellitus in a
human population. Furthermore, bitter-tasting compounds can
18 | AChemS Abstracts 2010
Abstracts are printed as submitted by the author(s)