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

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.