PROGRAM IN NEUROSCIENCE 
The Institute's Program in Neuroscience was es- 
tablished in 1984 in recognition of the challenging 
biomedical questions and research opportunities 
posed by the human brain and its function. Much of 
the research in this program is focused on the ways 
in which nerve cells conduct signals and communi- 
cate with each other and with the effector tissues of 
the body (such as muscle and gland cells), on the 
cellular mechanisms involved in the development 
of the nervous system, and most recently, on cogni- 
tive neuroscience and the computational capacity of 
complex neural networks. 
Investigators in the neuroscience program area 
are working at Johns Hopkins University, Massachu- 
setts General Hospital in Boston, the Massachusetts 
Institute of Technology, the University of Texas 
Southwestern Medical Center at Dallas, Yale Univer- 
sity, Columbia University, New York University, 
Stanford University, the California Institute of Tech- 
nology, the Salk Institute for Biological Studies, the 
University of Washington in Seattle, the State Univer- 
sity of New York at Stony Brook, Rockefeller Univer- 
sity, Brandeis University in Waltham, and the Uni- 
versity of California at Berkeley, Los Angeles, San 
Diego, and San Francisco. 
Neurons communicate with each other and with 
other cells through small molecules, the neurotrans- 
mitters. This communication occurs at specialized 
contact zones, the synapses. At the synapse, one cell 
(the presynaptic neuron) sends out a chemical sig- 
nal that is recognized by the second, postsynaptic 
cell by means of receptors. This process of neuro- 
transmission represents one of the bases for infor- 
mation processing in the brain. Neurotransmission 
is subject to extensive regulation that includes some 
forms of learning and memory, and disturbances of 
neurotransmission are thought to be involved in sev- 
eral diseases of the nervous system. 
The laboratory of Investigator Thomas C. Siidhof, 
M.D. (University of Texas Southwestern Medical 
Center at Dallas) is studying how cells form presyn- 
aptic nerve terminals and how the nerve terminals 
send out chemical signals at synapses. The work fo- 
cuses on the cellular organelles in the presynaptic 
cells that store the chemical signals used for synap- 
tic communication. Experiments are designed to 
determine how the chemical signals are released, 
how this release is regulated, and how this release is 
targeted exclusively to the site of the cell where the 
postsynaptic nerve cell awaits the signal. The work 
has led to the characterization of several novel pro- 
teins in the presynaptic cell that are likely to be 
involved in neurotransmission. In addition, a new 
family of cell surface receptors that may function in 
determining specific connections between cells has 
also been discovered. The results are relevant for 
understanding basic cellular processes (such as how 
cells secrete chemicals) as well as for insight into 
complex physiological processes (such as learning 
and memory) . 
The research in the laboratory of Associate Inves- 
tigator Richard L. Huganir, Ph.D. (Johns Hopkins 
University) is directed toward the understanding of 
the molecular mechanisms that underlie the modu- 
lation of synaptic function. Specifically, this group 
is investigating the role of protein phosphorylation 
in the regulation of neurotransmitter receptor func- 
tion. The laboratory has used the nicotinic acetyl- 
choline receptor, the prototypic neurotransmitter 
receptor, as a model system and has found that the 
nicotinic receptor is phosphorylated at seven differ- 
ent sites by three different protein kinases. Phos- 
phorylation of the nicotinic acetylcholine receptor 
enhances its desensitization to its neurotransmitter, 
acetylcholine. The phosphorylation (and thus the 
desensitization) of the nicotinic receptor by these 
three protein kinase systems is under the control of 
at least three neurotransmitters. In addition, recent 
results have suggested that tyrosine phosphoryla- 
tion of the receptor may regulate receptor aggrega- 
tion at the synapse during its formation. Dr. Hu- 
ganir's laboratory has also been investigating the 
role of protein phosphorylation in the regulation of 
the major excitatory and inhibitory neurotransmit- 
ter receptors in the brain, the glutamate receptors 
and GABA^ receptors. Results suggest that protein 
phosphorylation of neurotransmitter receptors is 
one of the major mechanisms in the modulation of 
their function and may play an important role in 
synaptic plasticity, such as long-term potentiation 
and long-term depression. 
Investigator Pietro De Camilli, M.D. (Yale Univer- 
sity) and his colleagues are interested in elucidating 
the traffic of synaptic vesicles (SVs) in neurons. 
Work carried out during the past year has provided 
further support for the hypothesis that SVs represent 
the neuronal adaptation of organelles found also in 
endocrine cells: synaptic-like microvesicles. It was 
shown that synaptic-like microvesicles of |8 cells 
store the neurotransmitter GABA. A GDP-releasing 
protein that may play a role in exocytosis from mam- 
malian cells, including neurons, was identified and 
NEUROSCIENCE 377 
