TY - JOUR
T1 - Impaired long-term depression in P2X3 deficient mice is not associated with a spatial learning deficit
AU - Wang, Yue
AU - Mackes, Jennifer
AU - Chan, Stephen
AU - Haughey, Norman J.
AU - Guo, Zhihong
AU - Ouyang, Xin
AU - Furukawa, Katsutoshi
AU - Ingram, Donald K.
AU - Mattson, Mark P.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/12
Y1 - 2006/12
N2 - The hippocampus is a brain region critical for learning and memory processes believed to result from long-lasting changes in the function and structure of synapses. Recent findings suggest that ATP functions as a neurotransmitter or neuromodulator in the mammalian brain, where it activates several different types of ionotropic and G protein-coupled ATP receptors that transduce calcium signals. However, the roles of specific ATP receptors in synaptic plasticity have not been established. Here we show that mice lacking the P2X3 ATP receptor (P2X3KO mice) exhibit abnormalities in hippocampal synaptic plasticity that can be restored by pharmacological modification of calcium-sensitive kinase and phosphatase activities. Calcium imaging studies revealed an attenuated calcium response to ATP in hippocampal neurons from P2X3KO mice. Basal synaptic transmission, paired-pulse facilitation and long-term potentiation are normal at synapses in hippocampal slices from P2X3KO. However, long-term depression is severely impaired at CA1, CA3 and dentate gyrus synapses. Long-term depression can be partially rescued in slices treated with a protein phosphatase 1-2 A activator or by postsynaptic inhibition of calcium/calmodulin-dependent protein kinase II. Despite the deficit in hippocampal long-term depression, P2X3KO mice performed normally in water maze tests of spatial learning, suggesting that long-term depression is not critical for this type of hippocampus-dependent learning and memory.
AB - The hippocampus is a brain region critical for learning and memory processes believed to result from long-lasting changes in the function and structure of synapses. Recent findings suggest that ATP functions as a neurotransmitter or neuromodulator in the mammalian brain, where it activates several different types of ionotropic and G protein-coupled ATP receptors that transduce calcium signals. However, the roles of specific ATP receptors in synaptic plasticity have not been established. Here we show that mice lacking the P2X3 ATP receptor (P2X3KO mice) exhibit abnormalities in hippocampal synaptic plasticity that can be restored by pharmacological modification of calcium-sensitive kinase and phosphatase activities. Calcium imaging studies revealed an attenuated calcium response to ATP in hippocampal neurons from P2X3KO mice. Basal synaptic transmission, paired-pulse facilitation and long-term potentiation are normal at synapses in hippocampal slices from P2X3KO. However, long-term depression is severely impaired at CA1, CA3 and dentate gyrus synapses. Long-term depression can be partially rescued in slices treated with a protein phosphatase 1-2 A activator or by postsynaptic inhibition of calcium/calmodulin-dependent protein kinase II. Despite the deficit in hippocampal long-term depression, P2X3KO mice performed normally in water maze tests of spatial learning, suggesting that long-term depression is not critical for this type of hippocampus-dependent learning and memory.
KW - Long-term depression
KW - Long-term potentiation
KW - P2X3KO mice
KW - Paired-pulse facilitation
KW - Water maze
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U2 - 10.1111/j.1471-4159.2006.04198.x
DO - 10.1111/j.1471-4159.2006.04198.x
M3 - Article
C2 - 17074061
AN - SCOPUS:33750925171
SN - 0022-3042
VL - 99
SP - 1425
EP - 1434
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 5
ER -