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Modulation of hippocampal calcium signalling and plasticity by serine/threonine protein phosphatases
Author(s) -
Koss David J.,
Hindley Kathleen P.,
Riedel Gernot,
Platt Bettina
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04579.x
Subject(s) - long term potentiation , okadaic acid , nmda receptor , phosphatase , synaptic plasticity , neurotransmission , biology , phosphorylation , dephosphorylation , hippocampal formation , microbiology and biotechnology , chemistry , neuroscience , biochemistry , receptor
Kinases and phosphatases act antagonistically to maintain physiological phosphorylation/dephosphorylation at numerous intracellular sites critical for neuronal signalling. In this study, it was found that inhibition of serine/threonine phosphatases by exposure of hippocampal slices to okadaic acid (OA) or cantharidin (CA; 100 nmol/L) for 2 h resulted in reduced basal synaptic transmission and blocked the induction of synaptic plasticity in the form of long‐term potentiation as determined by electrophysiological analysis. Fura‐2 Ca 2+ imaging revealed a bidirectional modulation of N ‐methyl‐ d ‐aspartate (NMDA) ‐mediated Ca 2+ responses and reduced KCl‐mediated Ca 2+ responses in neonatal cultured hippocampal neurons after phosphatase inhibition. While OA inhibited NMDA‐induced Ca 2+ influx both acutely and after incubation, CA‐enhanced receptor‐mediated Ca 2+ signalling at low concentrations (1 nmol/L) but reduced NMDA and KCl‐mediated Ca 2+ responses at higher concentrations (100 nmol/L). Changes in Ca 2+ signalling were accompanied by increased phosphorylation of cytoskeletal proteins tau and neurofilament and the NMDA receptor subunit NR1 in selective treatments. Incubation with OA (100 nmol/L) also led to the disruption of the microtubule network. This study highlights novel signalling effects of prolonged inhibition of protein phosphatases and suggests reduced post‐synaptic signalling as a major mechanism for basal synaptic transmission and long‐term potentiation impairments.