Selective modulation of some forms of schaffer collateral-CA1 synaptic plasticity in mice with a disruption of the CPEB-1 gene.
CPEB-1 is a sequence-specific RNA binding protein that stimulates the polyadenylation-induced translation of mRNAs containing the cytoplasmic polyadenylation element (CPE). Although CPEB-1 was identified originally in Xenopus oocytes, it has also been found at postsynaptic sites of hippocampal neurons where, in response to N-methyl-D-aspartate receptor activation, it is thought to induce the polyadenylation and translation of alphaCaMKII and perhaps other CPE-containing mRNAs. Because some forms of synaptic modification appear to be influenced by local (synaptic) protein synthesis, we examined long-term potentiation (LTP) in CPEB-1 knockout mice. Although the basal synaptic transmission of Schaffer collateral-CA1 neurons was not affected in the knockout mice, we found that there was a modest deficit in LTP evoked by a single train of 100 Hz stimulation, but a greater deficit in LTP evoked by one train of theta-burst stimulation. In contrast, LTP evoked by either four trains of 100 Hz stimulation or five trains of theta-burst stimulation were not or were only modestly affected, respectively. The deficit in LTP evoked by single stimulation in knockout mice appeared several minutes after tetanic stimulation. Long-term depression (LTD) evoked by 1 Hz stimulation was moderately facilitated; however, a stronger and more enduring form of LTD induced by paired-pulse 1 Hz stimulation was unaffected. These data suggest that CPEB-1 contributes in the translational control of mRNAs that is critical only for some selected forms of LTP and LTD.
Alarcon
Juan M
JM
College of Physicians and Surgeons of Columbia University, Columbia University, New York, New York 10032, USA. jma129@columbia.edu
Hodgman
Rebecca
R
Theis
Martin
M
Huang
Yi-Shuian
YS
Kandel
Eric R
ER
Richter
Joel D
JD
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020123:Sirolimus / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D000963:Antimetabolites; C490388:Cpeb1 protein, Xenopus; C490387:Cpeb1 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D012313:RNA; D020123:Sirolimus