RT Journal Article SR Electronic T1 Expression of long-term adaptation of synaptic transmission requires a critical period of protein synthesis JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 1099 OP 1109 DO 10.1523/JNEUROSCI.10-04-01099.1990 VO 10 IS 4 A1 PV Nguyen A1 HL Atwood YR 1990 UL http://www.jneurosci.org/content/10/4/1099.abstract AB 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.