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Lippiello, P.a , Hoxha, E.b c , Speranza, L.d , Volpicelli, F.a d , Ferraro, A.a , Leopoldo, M.e , Lacivita, E.e , Perrone-Capano, C.a d , Tempia, F.b c , Miniaci, M.C.a

The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK
(2016) Neuropharmacology, 101, pp. 426-438. Cited 1 time.
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84945555258&partnerID=40&md5=a270d224a8d0453816b233f15e36d21a
DOI: 10.1016/j.neuropharm.2015.10.019
AFFILIATIONS: aDepartment of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, Naples, Italy; 
bDepartment of Neuroscience, University of Torino, Torino, Italy; 
cNeuroscience Institute Cavalieri Ottolenghi (NICO), Torino, Italy; 
dInstitute of Genetics and Biophysics adriano Buzzati Traverso, CNR, Naples, Italy; 
eDepartment of Pharmacy - Drug Science, University of Bari a. Moro, Italy
ABSTRACT: The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signaling mechanisms have never been described. Using patch-clamp recordings in cerebellar slices of adult mice, we investigated the effects of a selective 5-HT7R agonist, LP-211, on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that 5-HT7R activation induces long-term depression of parallel fiber-Purkinje cell synapse via a postsynaptic mechanism that involves the PKC-MAPK signaling pathway. Moreover, a 5-HT7R antagonist abolished the expression of PF-LTD, produced by pairing parallel fiber stimulation with Purkinje cell depolarization; whereas, application of a 5-HT7R agonist impaired LTP induced by 1 Hz parallel fiber stimulation. Our results indicate for the first time that 5-HT7R exerts a fine regulation of cerebellar bidirectional synaptic plasticity that might be involved in cognitive processes and neuropsychiatric disorders involving the cerebellum. © 2015 Elsevier Ltd. All rights reserved.
AUTHOR KEYWORDS: 5-HT7 receptor;  Cerebellum;  Long-term depression;  Purkinje cell;  Serotonin;  Synaptic transmission
DOCUMENT TYPE: Article