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Evidence that caspase‐1 is a negative regulator of AMPA receptor‐mediated long‐term potentiation at hippocampal synapses
Author(s) -
Lu Chengbiao,
Wang Yue,
Furukawa Katsutoshi,
Fu Weiming,
Ouyang Xin,
Mattson Mark P.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03800.x
Subject(s) - ampa receptor , long term potentiation , neuroscience , hippocampal formation , excitatory postsynaptic potential , synaptic plasticity , microbiology and biotechnology , glutamate receptor , long term depression , postsynaptic potential , chemistry , silent synapse , biology , receptor , inhibitory postsynaptic potential , biochemistry
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.