Evidence that caspase-1 is a negative regulator of AMPA receptor-mediated long-term potentiation at hippocampal synapses

Chengbiao Lu, Yue Wang, Katsutoshi Furukawa, Weiming Fu, Xin Ouyang, Mark P. Mattson

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Best known for their pivotal role in a form of programmed cell death called apoptosis, caspases may also function in more subtle physiological processes. Caspases are present in synapses and dendrites of neurons where they can be activated in response to glutamate receptor stimulation and calcium influx. Here we tested the hypothesis that caspase-1 plays a role in modulating long-term potentiation (LTP) at hippocampal synapses. We provide evidence that caspase-1 plays a role in regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated calcium influx and synaptic plasticity in the hippocampus. LTP of excitatory postsynaptic potentials at CA1 synapses was significantly enhanced when hippocampal slices were treated with either a pan-caspase inhibitor or a selective inhibitor of caspase-1, but not by an inhibitor of caspase-6. Inhibition of caspase-1 significantly enhanced the AMPA current-mediated component of LTP without affecting the N-methyl-d-aspartate current-mediated component. Calcium responses to AMPA were enhanced in hippocampal neurons treated with a caspase-1 inhibitor suggesting that caspase-1 normally functions to reduce AMPA receptor-mediated calcium influx. These findings suggest that, by selectively reducing AMPA currents and calcium influx, caspase-1 functions as a negative regulator of LTP at hippocampal synapses.

Original languageEnglish
Pages (from-to)1104-1110
Number of pages7
JournalJournal of Neurochemistry
Volume97
Issue number4
DOIs
Publication statusPublished - 2006 May 1

Keywords

  • Apoptosis
  • Calcium
  • Dendrite
  • Learning
  • NMDA
  • Patch clamp

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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