eling the visual system has focused on two proper- 
ties of visual stimuli — disparity and motion. During 
the development of the visual cortex, cortical neu- 
rons are sensitive to correlations in the electrical 
activity coming from the two eyes. The laboratory 
studied a computer model for the development of 
disparity-selective cells in the visual cortex that de- 
pended on prenatal and postnatal phases. The model 
mimicked the observed relationship between dis- 
parity and ocular dominance. Models were also ex- 
amined for the representation of egocentric distance 
in a population of disparity-tuned neurons that re- 
ceive eye vergence signals. The neurons in area MT 
of monkeys respond selectively to the motion of vi- 
sual stimuli, but the same neurons are also tuned for 
other properties such as spatial frequency and dis- 
parity. A new approach to the integration of motion 
signals in area MT was introduced that depends on 
estimating the reliability of the local motion infor- 
mation. These estimates can be made by a separate 
population of neurons whose properties are pre- 
dicted by the model. 
Associate Investigator David P. Corey, Ph.D. (Mas- 
sachusetts General Hospital) and his colleagues 
have been studying the processes whereby the ion 
channels in the sensory receptor cells of the inner 
ear are activated in response to sound. In the past 
year this laboratory has found that the adaptation 
mechanism in vertebrate hair cells of the inner ear 
only works over a narrow range. The structure re- 
sponsible for adaptation is apparently the density 
marking the tip-link attachment site, since it moves 
with adaptation but its movement is limited. In 
other work the inherited human disease, hyperkale- 
mic periodic paralysis, was shown by several criteria 
to be caused by a defective sodium channel in 
muscle. 
The laboratory of Investigator Richard Axel, M.D. 
(Columbia University) is interested in the sense of 
smell. Mammals possess an olfactory system with 
enormous discriminatory power. How are the diver- 
sity and specificity of olfactory perception accom- 
plished? In initial experiments to define the logic 
underlying olfactory perception, Drs. Axel and 
Linda Buck identified and cloned a large family of 
genes that are likely to encode odorant receptors in 
vertebrates. Analysis of the structure of this large 
gene family and examination of the patterns of ex- 
pression provide insight into the mechanism by 
which the olfactory system can recognize a diverse 
array of odorants and how the brain can discriminate 
among different odors. 
The mammalian olfactory system can discriminate 
among more than 10,000 different odors at concen- 
trations as low as a few parts per trillion in air. The 
laboratory of Associate Investigator Randall R. Reed, 
Ph.D. (Johns Hopkins University) has identified sev- 
eral of the proteins thought to be responsible for 
signal transduction in the olfactory system. Olfac- 
tion and vision are thought to share analogous bio- 
chemical mechanisms for converting external stim- 
uli into electrical signals. The pathway for olfactory 
signal transduction appears to utilize a G protein 
cascade coupled to adenylyl cyclase. This laboratory 
has identified specialized forms of G proteins, ade- 
nylyl cyclase, and ion channels that are believed to 
mediate olfactory signal transduction. A recently de- 
scribed family of G protein-coupled receptors may 
contribute to the diversity in ligand recognition as- 
sociated with this sensory system. Recently this 
group has examined the subcellular localization of 
these putative receptors and the patterns of expres- 
sion of individual members of this gene family in 
olfactory epithelium. The laboratory also uses mo- 
lecular components of mammalian signal transduc- 
tion pathways as probes to identify homologues in 
the genetically manipulable organism Drosophila 
melanogaster. 
Research in the laboratory of Associate Investiga- 
tor Steven A. Siegelbaum, Ph.D. (Columbia Univer- 
sity) concerns the mechanisms whereby intracellu- 
lar second messenger molecules regulate neuronal 
function by controlling the activity of membrane 
ion channels. During the past year this group has 
focused on studies of cyclic nucleotide-gated chan- 
nels involved in olfactory signal transduction. They 
have characterized the properties of a cloned cyclic 
nucleotide-gated channel from catfish olfactory 
neurons and have compared the properties of the 
cloned channel expressed in Xenopus oocytes with 
the native channel in catfish olfactory neurons. 
In addition, they have shown that the cyclic 
nucleotide-gated channel becomes less active when 
the intracellular calcium concentration is elevated. 
This inhibition is likely to play an important role in 
sensory adaptation, a process in which a maintained 
exposure to an odorant leads to a decline in 
response. 
The superfamily of seven-transmembrane domain 
receptors linked to G proteins provides a major bio- 
logical mechanism for detecting intercellular and 
environmental signals. Because the receptors are of- 
ten situated at control points for crucial cellular ac- 
tivities, understanding the molecular basis of how 
ligands interact with them is important for the devel- 
opment of therapeutically useful chemicals. To ad- 
dress this problem. Associate Investigator Michael 
R. Lerner, M.D., Ph.D. (Yale University) and his 
colleagues have developed a versatile G protein- 
coupled, receptor bioassay. It is based on melano- 
NEUROSCIENCE 381 
