Persistent LTP without triggered protein synthesis.
Protein synthesis is believed to be involved in stabilizing synaptic plasticity. Effects lasting longer than about 2-3h are considered to require synthesis of new proteins, implying a functional separation between early (E) and late (L) components. However, the issue of constitutive vs. new protein synthesis is still unclear, especially in young animals. Here, we examined the effects of two protein synthesis inhibitors, anisomycin and emetine, on long-term-potentiation (LTP) in CA1 area of hippocampal slices from 12- to 20-day-old rats. Either drug was applied from -30 min to +30 min with respect to LTP induction, a time window previously reported to be critical. However, the LTP remained stable under the entire recording period of 4h (anisomycin), or 8h (emetine). Proper preparation of emetine solution was evidenced by the fact that, in separate experiments, prolonged treatment with emetine gradually blocked baseline responses. Although no corresponding effect was observed with anisomycin, the drug was judged to be potent by its ability to inhibit yeast growth. The ability of anisomycin to inhibit protein synthesis was further confirmed by radiolabeling experiments assessing the degree of leucine incorporation. Our data suggest that LTP up to at least 8h is not dependent on triggered protein synthesis but can be attained by utilizing proteins already available at induction time.
Abbas
Abdul-Karim
AK
Department of Medical Biophysics, Institute of Neuroscience and Physiology, Gothenburg University, Box 433, 40530 Gothenburg, Sweden. karim.abbas@physiol.gu.se
Dozmorov
Mikhail
M
Li
Rui
R
Huang
Fen-Sheng
FS
Hellberg
Fredrik
F
Danielson
Jonas
J
Tian
Ye
Y
Ekström
Jörgen
J
Sandberg
Mats
M
Wigström
Holger
H
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D004334:Drug Administration Schedule; D004640:Emetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D000841:Anisomycin; D007930:Leucine; D004640:Emetine