Journal of Neuroscience, Vol 10, 1099-1109, Copyright © 1990 by Society for Neuroscience
Expression of long-term adaptation of synaptic transmission requires a critical period of protein synthesis
PV Nguyen and HL Atwood
Department of Physiology, University of Toronto, Ontario, Canada.
The crayfish claw closer muscle is innervated by 2 distinct excitatory
motoneurons, one tonic and the other phasic. The phasic motoneuron is
relatively inactive and generates large EPSPs that normally depress rapidly
with repetitive stimulation at moderate frequencies. Stimulation of the
phasic motoneuron in vivo for 3 d at 5 Hz (2 hr/d) produced a marked
adaptive shift in the neuromuscular synaptic response properties of the
motoneuron: average initial EPSPs and depression of EPSPs were
significantly reduced. We tested the hypothesis that neuronal protein
synthesis is required for full expression of long-term adaptation (LTA). A
reversible inhibitor of neuronal protein synthesis, cycloheximide (CHX),
was injected into intact crayfish at various times prior to, during, or
after each stimulation period. At a dosage of 5 micrograms/gm body weight,
CHX inhibited the incorporation of [35S]- methionine into abdominal nerve
cord protein for approximately 2 hr after administration (greater than 80%
inhibition). Full expression of LTA was selectively blocked when CHX was
administered 6 hr or 2 hr prior to each stimulation period. Both the
reduction in initial EPSP amplitude and the resistance to synaptic
depression were significantly attenuated. CHX administered at the onset of
or at the end of each stimulation period did not affect the expression of
LTA. Control experiments using unstimulated animals showed that neither
chronic nor acute administration of CHX adversely affected the phasic
axon's synaptic response properties. Our results suggest that full
expression of neuronal LTA requires the presence of a pool of preexisting,
short- lived (or rapidly utilized) protein(s). Depletion of such a pool
prior to each stimulation period appears to interfere with subsequent
induction of LTA.