Selective Modulation of Some Forms of Schaffer Collateral-CA1 Synaptic Plasticity in Mice With a Disruption of the CPEB-1 Gene

  1. Juan M. Alarcon1,4,
  2. Rebecca Hodgman3,
  3. Martin Theis1,2,
  4. Yi-Shuian Huang3,
  5. Eric R. Kandel1,2, and
  6. Joel D. Richter3
  1. 1College of Physicians and Surgeons of Columbia University and 2Howard Hughes Medical Institute and Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA3 Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA

Abstract

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 αCaMKII 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.

Footnotes

  • Article and publication are at http://www.learnmem.org/cgi/doi/10.1101/lm.72704.

    • Accepted March 2, 2004.
    • Received November 21, 2003.
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