The Journal of Neuroscience, February 15, 2000, 20(4):1484-1494
Stimulus History Alters Behavioral Responses of Neuronal
Growth Cones
Thomas J.
Diefenbach,
Peter B.
Guthrie, and
Stanley B.
Kater
Department of Neurobiology and Anatomy, University of Utah School
of Medicine, Salt Lake City, Utah 84132
Generally, it is assumed that growth cones respond to a
specific guidance cue with a single, specific, and stereotyped
behavior. However, there is evidence to suggest that previous exposure
to a given cue might alter subsequent responses to that cue (Snow and
Letourneau, 1992; Shirasaki et al., 1998). We therefore tested the
hypothesis that growth cone responses to stimuli are dependent on the
history of previous stimulation. Growth cones of chick dorsal root
ganglion neurons were exposed to well characterized stimuli: (1)
contact with a laminin-coated bead, which causes growth cone turning,
or (2) electrical stimulation, which causes growth cone collapse.
Although the expected behavioral responses were observed after the
initial stimulation, strikingly different responses to a subsequent
stimulation were observed. Growth cones that had recovered from
electrical stimulation-induced collapse rapidly developed insensitivity
to a second identical electrical stimulation. Growth cones that
previously turned in response to contact with a laminin-coated bead
responded to a second bead with a "stall" or cessation in
outgrowth. This stimulus history dependence of growth cone behavior
could be generalized across dissimilar stimuli: after contact with a
laminin-coated bead, growth cones failed to collapse in response to
electrical stimulation. The calcium/calmodulin-dependent protein kinase
II (CaMKII) was implicated in this history dependence by
pharmacological experiments. Together, these results demonstrate that
growth cones can alter their behavioral response rapidly to a given
stimulus in a manner dependent on previous history and that knowledge
of past events in growth cone navigation may be required to predict
future growth cone behavior.
Key words:
growth cone; laminin; collapse; dorsal root ganglion; guidance; CaMKII
Copyright © 2000 Society for Neuroscience 0270-6474/00/2041484-11$05.00/0