The precise regulation of neural excitation is essential
for proper nerve cell, neural circuit, and nervous system
function. During postembryonic development and throughout
life, neurons are challenged with perturbations that
can alter excitability including changes in cell size,
innervation, and synaptic function. The cause of these
perturbations can be normal developmental changes associated
with our ability to learn and remember, or they can
be associated with disease or injury to the nervous
system. An increasing number of experiments demonstrate
that neurons are able to compensate for these types
of perturbation and maintain appropriate levels of excitation.
This type of compensation whereby a neuron is able to
return to a normal state of excitation is, by definition,
homeostasis. The mechanisms of homeostatic compensation
within the nervous system are diverse including changes
to synapse size, synaptic function, and ion channel
function. The implicit importance of homeostasis to
the appropriate function of the nervous system suggests
that there will be links to neural disease. Ultimately,
a thorough understanding of homeostatic signaling in
the nervous system at a cellular and molecular level
will be required to before we can establish links between
impaired homeostasis and diseases of the nervous system.
This is a major goal for my laboratory.
We are taking advantage of the powerful genetic tools
available in Drosophila to identify genes and signaling
pathways that are essential to the homeostatic regulation
of synaptic structure and function. These experiments
incorporate genetics, synaptic electrophysiology, imaging
and molecular studies. To date we have identified a
group of approximately 30 genes that may be involved
in the mechanisms of homeostasis in the nervous system.
We are in the process of characterizing the function
of many of these genes. Many of the genes we have identified
have clear homologues in the vertebrate genome. Ultimately,
we hope to define both the logic of homeostatic regulation
in the nervous system and the identity of the underlying
signaling systems. Our goal is to pursue the potential
cause and cure for neural disease and dysfunction.