High-Throughput Screens for Assessing Taste Sensitivity
in Mice
P.I.: John I.
Glendinning1
Co-P.I.: Alan
C. Spector2
Location and Contact Information:
1Department of Biological Science,
Barnard College
Columbia University
3009 Broadway
New York, NY 10027
phone: 212-854-4749
email: jglendinning@barnard.edu
2Department of Psychology,
University of Florida,
Gainesville, FL 32611
phone: 352-392-0601, x288
email: spector@psych.ufl.edu
Description: Humans suffer from a variety of taste disorders
that impair their ability to acquire essential nutrients, regulate secretion
of digestive enzymes, and enjoy one of life's simple pleasures: eating.
As there are few effective therapies for these disorders, the impending
comprehensive analysis of the mouse genome offers great promise for helping
fill this void. The ability of taste geneticists to identify genetically-based
alterations in murine taste sensitivity has been impeded by the absence
of a high-throughput screening protocol. Over the last decade, taste psychophysicists
have developed a high-throughput procedure for assessing taste sensitivity
in rats, called brief-access taste testing. Our goal is to adapt this
reliable, easy-to-use, and efficient procedure to mice.
Procedure: Mice are provided with access to a single taste
stimulus during brief (e.g., 5 sec) trials, and licking responses are
measured with an automated gustometer (see below). Using this device,
one can present several taste stimuli (e.g., different concentrations
of sucrose) during a 30-min test session in a randomized order, derive
a robust concentration-response function, and be relatively confident
that the licking responses are under orosensory control and not confounded
by postingestive effects of the taste stimulus. To this end, a secondary
screen will be developed for testing wild-type and mutant C57BL/6 mice.
Because this screen will be conducted with an expansive array of concentrations
of several taste stimuli (e.g., quinine, NaCl, and sucrose), it will be
able to detect gross and subtle alterations in taste sensitivity in either
direction. On the basis of the knowledge gained through the development
of the secondary screen, critical concentrations will be chosen for a
primary screen to provide a relatively quick assessment of taste sensitivity.
Outliers identified with the primary screen can be subjected to the secondary
screen for confirmation. A normative data-base for both screens will be
established and made available to the scientific community. The assay
procedures developed will be applicable by a single laboratory technician
with limited experience.
Illustration of a gustometer, similar to the one we are
using. Once a mouse is placed in the test chamber, a shutter (not shown)
will open, providing the mouse with access to a spout though a small
slit (see right diagram). This gustometer can automatically position
up to 8 different taste stimuli in front of the slit by moving the stimulus
delivery system laterally in precise steps (see left diagram). All licks
to a drinking spout will be recorded by a high frequency AC contact
circuit (not shown). The dedicated computer system, which controls the
stimulus delivery system and records licks, is not shown.
Selected references illustrating use of the brief-access taste test in
rats:
1. Spector, A. C., Redman, R. and Garcea, M. (1996). The consequences
of gustatory nerve transection on taste-guided licking of sucrose and
maltose in the rat. Behavioral Neuroscience 110, 1096-1109.
2. Markison, S., St.John, S. J. and Spector, A. C. (1995). Glossopharyngeal
nerve transection does not compromise the specificity of taste-guided
sodium appetite in rats. American Journal of Physiology 269, R215-R221.
3. St. John, S. J., Garcea, M. and Spector, A. C. (1994). Combined, but
not single, gustatory nerve transection substantially alters taste-guided
licking behavior to quinine in rats. Behavioral Neuroscience 108, 131-140.