Protein phosphatases mediate depotentiation induced by high-intensity theta-burst stimulation.

Journal Article (Journal Article)

We have previously reported that varying stimulus intensity produces qualitatively different types of synaptic plasticity in area CA1 of hippocampal slices: brief low-intensity (LI) theta-burst (TB) stimuli induce long-term potentiation (LTP), but if the stimulus intensity is increased (to mimic conditions that may exist during seizures), LTP is not induced; instead, high-intensity (HI) TB stimuli erase previously induced LTP ("TB depotentiation"). We now have explored the mechanisms underlying TB depotentiation using extracellular field recordings with pharmacological manipulations. We found that TB depotentiation was blocked by okadaic acid and calyculin A (inhibitors of serine/threonine protein phosphatases PP1 and PP2A), FK506 (a specific blocker of calcineurin, a Ca(2+)/calmodulin (CaM) protein phosphatase), and 8-Br-cAMP (an activator of protein kinase A) with 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor). These results suggest that protein phosphatase pathways are involved in the TB depotentiation similar to other type of down-regulating synaptic plasticity such as low-frequency stimulation (LFS)-induced long-term depression (LTD) and depotentiation in the rat hippocampus. However, TB depotentiation and LFS depotentiation could have differential functional significance.

Full Text

Duke Authors

Cited Authors

  • Kang-Park, M-H; Sarda, MA; Jones, KH; Moore, SD; Shenolikar, S; Clark, S; Wilson, WA

Published Date

  • February 2003

Published In

Volume / Issue

  • 89 / 2

Start / End Page

  • 684 - 690

PubMed ID

  • 12574446

International Standard Serial Number (ISSN)

  • 0022-3077

Digital Object Identifier (DOI)

  • 10.1152/jn.01041.2001


  • eng

Conference Location

  • United States