Activity-Dependent Growth Cone Properties

Suny At Albany, Albany NY

Investigators

Abstract

Lay Summary Experience plays an important role in the development, maintenance, and modification of the nervous system. Activity-dependent changes in the nervous system are responsible for the strong effect of early experience on adult behavior and the modifications in behavior (learning) that continue throughout life. A major goal of brain research is to understand how electrical activity influences the properties of individual brain cells (neurons) and their interconnections (synapses) . It is very difficult to study single neurons and synapses in the vertebrate brain; this is much easier in the simpler invertebrate nervous system. In the crayfish neuromuscular system, single axons (elongated portion of the neuron), which form synaptic connections on the muscle, can be studied in the living animal or in a culture dish. Here axons with different levels of electrical activity develop differences in synaptic structure and function. The proposed research examines the activity-dependent development of intracellular calcium ([Ca2+]i) regulation and the formation of synaptic structures at the axon terminal: both of these are important for the release of neurotransmitter, the signal used at synapses. The regulation of [Ca2+]i is very important since [Ca2+]i also controls gene regulation, as well as neuronal growth and death. The developmental effect of electrical activity will be examined by removing the crayfish nerve cord and studying regenerating (developing) axons in a culture dish over a period of days. Pharmacological agents will be used to alter electrical activity, calcium influx, and perturb intracellular signal-transduction pathways. Calcium regulation will then be examined at the growing tip of the axon (growth cone) using fluorescent calcium indicators and electrophysiological techniques, and synaptic structures will be visualized with electron microscopy. To determine whether similar activity-dependent changes occur in mature axons, the electrical activity of axons will be altered in an intact, adult crayfish, and the axon terminal will again be examined. Findings from these studies will add to our knowledge of the basic mechanisms responsible for nervous system development. In particular, these results will further define the role of experience in specifying neuronal structure and function, and the range of adaptation of the nervous system to altered use.