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#43
PLATFORM PRESENTATIONS:
TASTE
Genetic deletion of ectoATPase reduces specific taste responses
Aurelie Vandenbeuch
1,3
, Catherine B Anderson
1,3
, Matthew
Streritz
1,3
, Jason A Parnes
2,3
, Simon C Robson
4
, Thomas E Finger
2,3
,
Sue C Kinnamon
1,3
1
Department of Otolaryngology, University of Colorado Denver
Aurora, CO, USA,
2
Department of Cell and Development Biology,
University of Colorado Denver Aurora, CO, USA,
3
Rocky Mountain
Taste and Smell Center Aurora, CO, USA,
4
Beth Israel Deaconess
Medical Center Boston, MA, USA
In taste buds, ATP is crucial in the transmission of the taste signal
from sensory cells to nerve fibers. ATP is released from Type II
taste cells via hemichannels in response to taste stimulation and
activates ionotropic P2X receptors on afferent nerve endings as
well as metabotropic P2Y receptors on Type II and Type III taste
cells. The released ATP is then degraded to ADP by the specific
ectoATPase, NTPDase2, present in the membrane of Type I cells.
To determine if ectonucleotidases play a role in taste function, we
examined responses to taste stimuli in NTPDase2 knockout mice.
Although taste buds are present in the knockout mice and appear
morphologically normal, they completely lack ectoATPase activity,
as assessed by histochemical staining with both ATP and ADP as
substrates. Thus, these mutant mice should have decreased
breakdown of the released ATP, resulting in a longer lifetime of
ATP in the extracellular space surrounding taste buds. To determine
if the persistence of ATP affects taste function, we recorded from
the chorda tympani nerve in response to a battery of taste stimuli.
Interestingly, responses to sweet and umami stimuli were
profoundly depressed in knockout mice compared to wild type
mice, although responses to non-specific electrolytes and sour
stimuli were similar in knockout and wild type mice. Preliminary
behavioral tests confirmed the lack of response to sweet stimuli,
suggesting that the prolonged presence of ATP in extracellular
space may desensitize P2X receptors on the chorda tympani nerve
fibers, particularly those that respond to sweet and umami stimuli.
Alternatively, the lack of generated ADP may modulate the
sensitivity of Type II cells to taste stimuli. Acknowledgements:
Supported by NIH grants R01DC007495 and P30DC004657.
#44
PLATFORM PRESENTATIONS:
TASTE
Bitter taste stimuli induce differential neural codes in the
mouse brain
Christian H Lemon
1
, David M Wilson
1
, John D Boughter, Jr.
2
1
St. Louis University School of Medicine Saint Louis, MO, USA,
2
University of Tennessee Health Science Center Memphis, TN, USA
A growing literature suggests tastants commonly assigned to
the “bitter” category induce heterogeneous neural and perceptual
responses. Here we electrophysiologically recorded taste activity
(spikes) to bitter stimuli from nucleus tractus solitarii neurons in
isogenic inbred C3HeB/FeJ mice and a congenic mouse line bred
to be homozygous at a genetic locus influencing bitter taste.
Using these mice allowed removal of genetic heterogeneity as a
factor influencing bitter responses. Stimuli (26 total) included
concentration series of quinine (QUI), denatonium (DEN),
cycloheximide (CYX), sucrose octaacetate (SOA), and other taste
stimuli, all delivered “whole mouth” for 5 s then rinsed. 79 neurons
were tested with all stimuli; in many cases multiple cells (2 to 5)
were recorded from single mice. Results showed “bitter” stimuli
induced variable responses. For example, although some neurons
possessed robust responses to QUI, DEN, and CYX, other cells
displayed concentration dependent activity (
P
<0.05) to QUI and
DEN, but not CYX. Differential “bitter” activity was found across
bitter-sensitive cells recorded from the same mouse, indicating that
variability in bitter responses exist in individual animals.
Multivariate analyses of responses showed that QUI and DEN
induced correlated spatial patterns that differed from those to CYX
and SOA. A higher resolution multivariate approach applied to
sequential 500 ms bins of activity across concentrations/trials
revealed response patterns to QUI/DEN and CYX/SOA diverged
during only the initial ~1.5 s of the taste response. Activity to all
“bitters” converged to a common pattern in follower epochs. Our
findings extend data suggesting differences among “bitter” taste
codes, data which challenge a strict monoguesia model for the
bitter quality. Acknowledgements: NIH DC011579 (C.H.L.)
#45
PLATFORM PRESENTATIONS:
TASTE
Deletion or Inhibition of Trpm5 Decreases the Gain in Body
Weight and Fat Mass in Mice
Sami Damak, Johannes le Coutre, Carole Bezençon
Nestlé Research Center Lausanne, Switzerland
Receptors and downstream signal transduction molecules involved
in taste signalling on the tongue are also expressed in the
gastrointestinal tract. Trpm5, a calcium activated ion channel
necessary for sweet, bitter and
umami
taste transduction, is also
strongly expressed in solitary cells distributed throughout the
gastrointestinal tract. Here, we show that Trpm5 knockout mice are
leaner than their wild type littermates. A similar effect is obtained
by feeding mice quinine, an inhibitor of Trpm5. Compared with
mice consuming AIN, a regular balanced diet, mice consuming
AIN diet supplemented with 0.1% quinine gain less fat mass
(1.61g
vs
3.35g) after 12 weeks of diet, with identical increase
in lean mass, and have lower blood glucose and plasma
triglycerides. No difference is observed in food intake, activity
or energy expenditure between treatment and control. Quinine fed
mice do not regain weight up to one month after removal of quinine
from the diet. The consumption of quinine led to only a small
decrease in fat mass gain in Trpm5 knockout mice compared to
Trpm5 knockout mice consuming regular diet (1.38g
vs
2.14g),
indicating that the effect of quinine is largely Trpm5-
dependent. Quinine treated wild type mice have higher faecal
energy and lipid contents than mice fed a regular diet, showing that
deregulated intestinal nutrient uptake contributes to the quinine-
induced decrease in weight gain.
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