|
RESEARCH OVERVIEW
This laboratory studies the cellular determinants of the
responses of inner ear vestibular organs with electrophysiological,
video, neurochemical, and genetic techniques. We employ the common pond
turtle (red-eared slider), toadfish, and transgenic mice for these
experiments.
Vestibular hair cells express a variety of transmitter phenotypes
including glutamate and GABA, and a variety of ionic channels. We are
investigating these and other features in relation to the dynamics of
synaptic transmitter release.
The major highlight of this years' work was the discovery the hair
bundles of the fish vestibular semicricular canals amplify the
mechanical signal to the canal. This is reflected in a non-linear
response for very low level angular velocity stimuli. In simple terms,
if one plots an input vs output curve for the semicircular canals the
curve is generally linear. I.e., an increment in angular velocity
results in an increment of hair cell response. If one extends this plot
through zero stimulus, a straight line is scribed. However, the actual
response of the fish deviates from linearity. For very low velocity
stimulus levels of, say 1-2 degrees per second, the response is greater
tat the prediction of the straight line. This is because the hair cell
hair bundles actually amplify the response for low level stimuli.
Interestingly, this response is under central nervous system control.
Namely, activation of the efferent vestibular system removes the
non-linearity and the input vs output curve now passes through zero. see PDF
In the organ of hearing, the mammalian cochlea there is also a
phenomenon called a compressional non-linearity wherein very low sound
level stimuli are amplified out of proportion to a linear response.
This compressional non-linearity is also controlled by the central
nervous system as activation of the efferent auditory system linearizes
the response.
It is amazing that the teleost fish evolved this mechanism 3-400
million years ago, long before mammals walked the earth. Apparently the
mammals co-opted this mechanism for their own nefarious ends, without
giving the fish any credit at all. Presently we are concentrating on
studies of the function of the post-synaptic calyx ending within the
vestibular epithelium by patch-clamping this ending. Basic scientific
study of the labyrinth may lead to potential therapies for clinical
conditions such as Meniere's syndrome.
http://hermes.mbl.edu/research/resident/lab_highstein.html
Contact Information:
Stephen M. Highstein, MD, PhD
Senior Scientist
Marine Biological Laboratory
MRC 205 & 207
7 MBL Street
Woods Hole, MA 02543
508-289-7318 and 7391; fax: 508-289-7900
shighstein@mbl.edu
|