Performance in long-term memory tasks is augmented by a phosphorylated growth factor receptor fragment
✍ Scribed by P.K. Dash; S.A. Mach; M.R. Moody; A.N. Moore
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 383 KB
- Volume
- 77
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
To elucidate the role of enhanced phosphoinositide‐3‐kinase (PI3‐kinase) activity in memory, a synthetic phosphopeptide (TAT‐Y^P^MDM) containing the p85 regulatory subunit receptor‐binding motif (YXXM) coupled to the cell transduction domain of HIV‐TAT protein was employed. This phosphopeptide bound the p85 subunit of PI3‐kinase, and was internalized by both granule and pyramidal neurons when injected into the hippocampus. Increased lipid kinase activity and enhanced phosphorylation of the PI3‐kinase substrates Akt (protein kinase B) and ribosomal S6 kinase were associated with TAT‐Y^P^MDM administration. Bilateral infusion of the phosphopeptide into the dorsal hippocampus after training improved performance in three hippocampus‐dependent memory tasks: contextual fear conditioning, trace fear conditioning, and the Morris water maze. Both the biochemical and behavioral effects of the TAT‐Y^P^MDM phosphopeptide could be blocked by wortmannin. No effect was observed when a nonphosphorylated peptide (TAT‐YMDM), or a second, unrelated phosphopeptide (TAT‐Y^P^LDL) was utilized. In addition, infusion of the TAT‐Y^P^MDM phosphopeptide did not interfere with memory acquisition or 4 hr memory. In addition, pretesting administration did not affect the ability to recall a previously established long‐term memory. These findings suggest that stimulation of PI3‐kinase activity by phosphorylated receptor fragments containing the YMDM motif augments long‐term memory. © 2004 Wiley‐Liss, Inc.