Molecular Structure and Function of Central Nervous System Synapses
are stored in the brain as connected neurons "encoding"
simultaneous events and impressions. Activation of one of
the connected neurons can lead to activation of all of them.
Formation of new memories requires the formation of new connections
among neurons. One way the brain accomplishes this is to strengthen
synapses among neurons that fire together during an event.
communicate through synapses that release chemical transmitters
to activate a target neuron. Many transmitters can also initiate
biochemical changes in the signaling machinery of the synapse itself.
The biochemical changes can either increase or decrease the size
of the signal produced by the synapse when it fires again. This
is called "synaptic plasticity."
brains have evolved complex mechanisms for controlling the circumstances
under which such changes will occur. For example, one of the
receptors for the excitatory amino acid glutamate (the NMDA-type
glutamate receptor), triggers an increase in the strength of an
active synapse only when simultaneous activation of several synapses
causes the postsynaptic neuron to fire an action potential. This
"plasticity rule" is used to form memories.
lab is studying biochemical signal transduction systems in central
nervous system synapses. We have focused on a complex of signaling
proteins, called the postsynaptic density (PSD), located just underneath
excitatory receptors in the central nervous system. We showed that
it contains signal transduction molecules that can control the sensitivity
of transmitter receptors, the size of receptor clusters, and perhaps
the integrity of the adhesion junction that holds presynaptic terminals
a combination of microchemical and recombinant DNA methods, we have
determined the structure of several proteins associated with the
PSD. We are presently studying the associations of these proteins
with each other and their specific roles in controlling synaptic
transmission. Our ultimate goal is to illuminate the ways
that synapses change their strength to encode memories.
many (we think most) of the important signaling molecules in the
PSD have now been identified and sequenced, we are turning our attention
to learning how they work together to create the delicate mechanisms
of synaptic plasticity. Thus, one aspect of our work involves
study of the functions of the signaling
machinery in the postsynaptic density. Another major aspect
is the development of computer
simulations of synaptic signaling to aid our understanding of
how the large number of signaling molecules present at the synapse
may work together.