Modulation of hippocampal calcium signalling and plasticity by serine/threonine protein phosphatases
Version of Record online: 16 MAR 2007
Journal of Neurochemistry
Volume 102, Issue 4, pages 1009–1023, August 2007
How to Cite
Koss, D. J., Hindley, K. P., Riedel, G. and Platt, B. (2007), Modulation of hippocampal calcium signalling and plasticity by serine/threonine protein phosphatases. Journal of Neurochemistry, 102: 1009–1023. doi: 10.1111/j.1471-4159.2007.04579.x
- Issue online: 16 MAR 2007
- Version of Record online: 16 MAR 2007
- Received January 15, 2007; revised manuscript received February 28, 2007; accepted March 1, 2007.
- Alzheimer’s disease;
- long-term potentiation;
- okadaic acid;
- synaptic transmission;
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 Ca2+ imaging revealed a bidirectional modulation of N-methyl-d-aspartate (NMDA) -mediated Ca2+ responses and reduced KCl-mediated Ca2+ responses in neonatal cultured hippocampal neurons after phosphatase inhibition. While OA inhibited NMDA-induced Ca2+ influx both acutely and after incubation, CA-enhanced receptor-mediated Ca2+ signalling at low concentrations (1 nmol/L) but reduced NMDA and KCl-mediated Ca2+ responses at higher concentrations (100 nmol/L). Changes in Ca2+ 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.