Journal
CEREBELLUM
Volume 12, Issue 3, Pages 297-299Publisher
SPRINGER
DOI: 10.1007/s12311-012-0444-9
Keywords
cPLA(2)alpha; Arachidonic acid; Purkinje cell; DSE; Long-term potentiation
Categories
Funding
- National Foundation of Natural Science of China [30600168, 31070945, 31100780, 31200818]
- Foundation of Zhejiang Educational Committee, China [Y201121662, Y20070109]
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Cytosolic phospholipase A(2) alpha (cPLA(2)alpha) responds to micromolar intracellular Ca2+ and produces arachidonic acid, which regulates cellular homeostasis, neurotoxicity, and inflammation. Endocannabinoids are the derivates of arachidonic acid and widely distributed in the cerebellum. However, the role of cPLA(2)alpha/arachidonic acid pathway in cerebellar synaptic transmission and plasticity is unknown. We utilized cPLA(2)alpha knockout mice and slice whole-cell patch clamp to study the action of cPLA(2)alpha/arachidonic acid signaling on the depolarization-induced suppression of excitation (DSE) and long-term potentiation at parallel fiber-Purkinje cell synapses. Our data showed that DSE was significantly inhibited but rescued by arachidonic acid in cPLA(2)alpha knockout mice. The degradation enzyme of 2-arachidonoylglycerol (2-AG), monoacylglycerol lipase, blocked DSE, while another catabolism enzyme for N-arachidonoylethanolamine, fatty acid amide hydrolase, did not, suggesting that 2-AG is responsible for DSE in Purkinje cells. Co-application of paxilline reversed the blockade of DSE by internal K+, indicating that large-conductance Ca2+-activated potassium channel is sufficient to inhibit cPLA(2)alpha/arachidonic acid-mediated DSE. On the other hand, we found that 1 Hz parallel fiber stimuli-triggered long-term potentiation (LTP) was deficient in cPLA(2)alpha knockout mice. LTP was also inhibited when AACOCF3, an inhibitor of cPLA(2)alpha, was given. Arachidonic acid was necessary for the LTP induction. Therefore, these data showed that cPLA(2)alpha/arachidonic acid/2-AG signaling pathway mediates DSE and LTP at parallel fiber-Purkinje cell synapse.
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