Calcium stores regulate the polarity and input specificity of synaptic modification

Makoto Nishiyama, Kyonsoo Hong, Katsuhiko Mikoshiba, Mu-ming Poo () and Kunio Kato
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Makoto Nishiyama: University of California at San Diego
Kyonsoo Hong: University of California at San Diego
Katsuhiko Mikoshiba: Mikoshiba Calciosignal Net Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation (JST)
Mu-ming Poo: University of California at San Diego
Kunio Kato: Mikoshiba Calciosignal Net Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation (JST)

Nature, 2000, vol. 408, issue 6812, 584-588

Abstract: Abstract Activity-induced synaptic modification is essential for the development and plasticity of the nervous system1,2,3. Repetitive correlated activation of pre- and postsynaptic neurons can induce persistent enhancement or decrement of synaptic efficacy, commonly referred to as long-term potentiation or depression2,3(LTP or LTD). An important unresolved issue is whether and to what extent LTP and LTD are restricted to the activated synapses4,5,6,7,8. Here we show that, in the CA1 region of the hippocampus, reduction of postsynaptic calcium influx by partial blockade of NMDA (N-methyl-d-aspartate) receptors results in a conversion of LTP to LTD and a loss of input specificity normally associated with LTP, with LTD appearing at heterosynaptic inputs. The induction of LTD at homo- and heterosynaptic sites requires functional ryanodine receptors and inositol triphosphate (InsP3) receptors, respectively. Functional blockade or genetic deletion of type 1 InsP3 receptors led to a conversion of LTD to LTP and elimination of heterosynaptic LTD, whereas blocking ryanodine receptors eliminated only homosynaptic LTD. Thus, postsynaptic Ca2+, deriving from Ca2+ influx and differential release of Ca2+ from internal stores through ryanodine and InsP3 receptors, regulates both the polarity and input specificity of activity-induced synaptic modification.

Date: 2000
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DOI: 10.1038/35046067

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