title: Na+ -Ca2+ exchanger (NCX3) knock-out mice display an impairment in hippocampal long-term potentiation and spatial learning and memory.
abstract: Long-term potentiation (LTP) depends on the coordinated regulation of an ensemble of proteins related to Ca(2+) homeostasis, including Ca(2+) transporters. One of the major players in the regulation of intracellular Ca(2+) ([Ca(2+)](i)) homeostasis in neurons is the sodium/calcium exchanger (NCX), which represents the principal mechanism of Ca(2+) clearance in the synaptic sites of hippocampal neurons. Because NCX3, one of the three brain isoforms of the NCX family, is highly expressed in the hippocampal subfields involved in LTP, we hypothesized that it might represent a potential candidate for LTP modulation. To test this hypothesis, we first examined the effect of ncx3 gene ablation on NCX currents (I(NCX)) and Ca(2+) homeostasis in hippocampal neurons. ncx3(-/-) neurons displayed a reduced I(NCX), a higher basal level of [Ca(2+)](i), and a significantly delayed clearance of [Ca(2+)](i) following depolarization. Furthermore, measurement of field EPSPs, recorded from the CA1 area, revealed that ncx3(-/-) mice had an impaired basal synaptic transmission. Moreover, hippocampal slices from ncx3(-/-) mice exhibited a worsening in LTP compared with congenic ncx3(+/+). Consistently, immunohistochemical and immunoblot analysis indicated that in the hippocampus of ncx3(-/-) mice both Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) expression and the phosphoCaMKIIα/CaMKIIα ratio were significantly reduced compared with ncx3(+/+). Interestingly, ncx3(-/-) mice displayed a reduced spatial learning and memory performance, as revealed by the novel object recognition, Barnes maze, and context-dependent fear conditioning assays. Collectively, our findings demonstrate that the deletion of the ncx3 gene in mice has detrimental consequences on basal synaptic transmission, LTP regulation, spatial learning, and memory performance.
authors: Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, 80131 Naples, Italy.
authors: Pasquale
authors: P
authors: Molinaro
authors: Davide
authors: D
authors: Viggiano
authors: Robert
authors: R
authors: Nisticò
authors: Rossana
authors: R
authors: Sirabella
authors: Agnese
authors: A
authors: Secondo
authors: Francesca
authors: F
authors: Boscia
authors: Anna
authors: A
authors: Pannaccione
authors: Antonella
authors: A
authors: Scorziello
authors: Bisan
authors: B
authors: Mehdawy
authors: Sophie
authors: S
authors: Sokolow
authors: André
authors: A
authors: Herchuelz
authors: Gianfranco F
authors: GF
authors: Di Renzo
authors: Lucio
authors: L
authors: Annunziato
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