tion. Dr. Reichardt is also studying certain mole- 
cules on the surfaces of cells and in the extracellu- 
lar matrix that serve as substrates for guiding the 
growth of axons. A third project seeks to identify 
molecules that direct neurons to form synapses 
with other cells. Since synapses are the sites of in- 
formation transfer between neurons, these mole- 
cules are also crucial in establishing the correct wir- 
ing of the nervous system. 
Understanding the molecular mechanisms by 
which the neuroendocrine system develops and by 
which neuropeptides and hormones control critical 
regulatory events is the central goal of the labora- 
tory of Investigator Michael G. Rosenfeld, M.D. 
(University of California at San Diego). Analysis of 
several hormone receptors has provided specific in- 
sights into the molecular mechanisms of signal 
transduction and hormonal regulation of gene ex- 
pression and has led to the identification of a class 
of transcriptional activators that exhibit precise 
temporal and spatial patterns of expression in the 
developing nervous and endocrine systems. An un- 
expected mechanism for post-transcriptional regu- 
lation in the brain has been mechanistically defined 
by the analysis of a gene encoding the calcitonin 
gene-regulated peptide, which is the most potent 
known vasodilator. 
Investigator Larry W Swanson, Ph.D. (The Salk 
Institute for Biological Studies) and his colleagues 
have been characterizing the functional organiza- 
tion of brain circuits that determine behavioral 
state in mammals. Recent work has focused on the 
mechanisms that underlie some of the dramatic ef- 
fects of the gonadal steroid hormone estrogen on 
the levels of a number of neuropeptides in neurons 
involved in reproductive behavior and physiology. 
They have also recently mapped the distribution of 
nicotinic acetylcholine receptors in the brain and, 
with Dr. Rosenfeld's group, have been localizing, 
within the brain, certain transcription factors that 
regulate gene expression. 
The exquisite sensitivity and specificity of the ol- 
factory system in the detection and discrimination 
of odors is remarkable. Associate Investigator Ran- 
dall R. Reed, Ph.D. (The Johns Hopkins University) 
and his colleagues have identified several of the 
proteins believed to be responsible for signal trans- 
duction in the olfactory system. Olfaction and vi- 
sion appear to share analogous biochemical mecha- 
nisms for converting external stimuli into electrical 
signals. The pathway for olfactory signal transduc- 
tion appears to utilize a G protein cascade coupled 
to adenylyl cyclase. Dr. Reed's laboratory has re- 
cently identified cDNA clones that encode several 
distinct forms of this enzyme. One of these, type III 
cyclase, is exclusively expressed in olfactory sensory 
neurons. To elucidate the role of the various forms 
of the mammalian enzyme, the group has identified 
homologues of several forms of adenylyl cyclase in 
the genetically manipulable organism Drosophila. 
Sex pheromones are specific chemicals that are 
released by certain animals in order to trigger in- 
nate mating behavior. The ability of the target ani- 
mal to respond to minuscule amounts of phero- 
mone depends on a highly sensitive detection 
system. This sensory system is under investigation 
by Assistant Investigator Michael R. Lerner, M.D., 
Ph.D. (Yale University) and his colleagues. A second 
interest of the laboratory is in the control of gene 
expression, particularly in the central nervous sys- 
tem, by differential pre-mRNA splicing. Small nu- 
clear ribonucleoproteins (snRNPs) are intimately 
associated with RNA processing in general. Many 
snRNPs in the central nervous system contain pro- 
tein, which appears to replace the general snRNP 
B protein. How this protein contributes to the 
mechanism of alternative splicing is being explored. 
The laboratory of Investigator King-Wai Yau, 
Ph.D. (The Johns Hopkins University) has contin- 
ued its effort to understand the visual transduction 
process by which light triggers an electrical signal 
in retinal photoreceptors. Recently they have been 
engaged in two kinds of studies. First, in an attempt 
to clarify a long-standing puzzle in vision, they have 
made a comprehensive study of the adaptation be- 
havior of rods in a variety of mammals and have 
found, contrary to widespread belief, that these 
cells behave much like those in lower vertebrates. 
Second, they have carried out an in-depth biophysi- 
cal study of the gating characteristics of the ion 
channel that mediates phototransduction in rods 
and cones. This work has provided kinetic informa- 
tion about the ion channels that are directly acti- 
vated by cyclic nucleotides, a unique and novel 
class of ion channels that includes the photo- 
transducing channel. 
The laboratory of Associate Investigator James B. 
Hurley, Ph.D. (University of Washington) continues 
to investigate the relationship between the bio- 
chemical properties of signal transducing G pro- 
teins and the physiological responses of the cells in 
which they are expressed. The group is comparing 
signal transduction pathways of retinal rods and 
cones to determine how differences between the 
signal transduction enzymes in these cells deter- 
mine their light sensitivity and response kinetics. 
Continued 
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