The Birren Lab is interested in understanding how embryonic precursor cells respond to local environmental cues during the development of the mammalian nervous system. We have focused on two developmental stages in the rat and murine peripheral nervous systems: the restriction of neural precursor cells to specific neuronal lineages and the development and function of synaptic connections.
Another
focus of the laboratory is to understand the role of target-derived
trophic
factors on the formation and function of synapses between sympathetic
neurons and heart tissue. Nerve growth factor (NGF), acting
through the trkA receptor tyrosine kinase, plays a role in the
development and survival sympathetic neurons. We have recently
demonstrated that NGF also acts to acutely potentiate synaptic
transmission between sympathetic neurons and cardiac myocytes in
culture. Cardiac myocytes beat spontaneously in culture. If a synaptic
connection exists between a neuron and a beating myocyte, electrical
stimulation of the neuron results in synaptic transmission between the
neuron and the myocyte and an increase in myocyte beat rate. This
culture system is analogous to the situation in the animal where
increased sympathetic input to the heart results in an increased heart
rate. Using this system, we have demonstrated that, in the presence of
NGF, stimulation of a neuron leads to a greater postsynaptic response
of a connected myocyte. We have demonstrated that NGF acts
presynaptically to mediate the level of synaptic transmission between
the neuron and its target. The finding that NGF acutely and reversibly
modulates synaptic transmission between sympathetic neurons and
myocytes raises the question of how synaptic activity, NGF and NGF
receptors interact to lead to long term changes in synaptic function.
Ongoing investigations in the laboratory are also addressing the
developmental role of NGF in the establishment of peripheral synaptic
connections. We have found that NGF acts as one signal in a series of
interactions between neurons and myocytes resulting in the development
of sympathetic presynaptic machinery.