title: Long-term potentiation at cerebellar parallel fiber-Purkinje cell synapses requires presynaptic and postsynaptic signaling cascades.
abstract: Long-term depression (LTD) and long-term potentiation (LTP) at cerebellar parallel fiber-Purkinje cell (PF-PC) synapses play critical roles in motor learning. The 1 Hz stimulation at PF-PC synapses induces a postsynaptically expressed LTP that requires a postsynaptic Ca(2+) transient, phosphatases, and nitric oxide (NO). However, the mechanism underlying 1 Hz PF-LTP remains unclear because none of the known events is related to each other. Here, we demonstrated that 1 Hz PF-LTP requires postsynaptic cytosolic phospholipase A2 α (cPLA2α)/arachidonic acid (AA) signaling and presynaptic endocannabinoid receptors. Using patch-clamp recording in cerebellar slices, we found that 1 Hz PF-LTP was abolished in cPLA2α-knock-out mice. This deficit was effectively rescued by the conjunction of 1 Hz PF stimulation and the local application of AA. 2-Arachidonoylglycerol and the retrograde activation of cannabinoid receptor 1 (CB1R) were also involved in 1 Hz LTP because it was blocked by the hydrolysis of 2-AG or by inhibiting CB1Rs. The amount of NO released was detected using an NO electrode in cultured granule cells and PF terminals. Our results showed that the activation of CB1Rs at PF terminals activated NO synthetase and promoted NO production. The 1 Hz PF-stimuli evoked limited NO, but 100 Hz PF stimulation generated a large amount. Therefore, 1 Hz PF-LTP, distinct from classical postsynaptically expressed plasticity, requires concurrent presynaptic and postsynaptic activity. In addition, NO of sufficient amplitude decides between the weakening and strengthening of PF-PC synapses.
authors: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China, and Neuroscience Care Unit, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310058 China.
authors: De-Juan
authors: DJ
authors: Wang
authors: Li-Da
authors: LD
authors: Su
authors: Ya-Nan
authors: YN
authors: Wang
authors: Dong
authors: D
authors: Yang
authors: Cheng-Long
authors: CL
authors: Sun
authors: Lin
authors: L
authors: Zhou
authors: Xin-Xin
authors: XX
authors: Wang
authors: Ying
authors: Y
authors: Shen
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005260:Female; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
keywords: Purkinje cell; arachidonic acid; cPLA2α; endocannabinoids; long-term potentiation; parallel fiber