Calcium Turning Depression into Potentiation

Repeated stimulation at a synapse can lead to long-term synaptic modifications [long-term potentiation (LTP) or long-term depression (LTD)] that may underlie the mechanisms of learning and memory. Nishiyama et al. found that LTP or LTD could be induced by paired stimuli to the pre- and postsynaptic cells, depending on the intervals between the stimulation to the presynaptic cell and the depolarizing spike induced in the postsynaptic cell. Additionally, LTP could be converted into LTD if N-methyl-D-aspartate glutamate receptors were partially blocked, and LTD could be converted into LTP if inositol triphosphate receptors (IP₃Rs) were blocked or missing (by genetic deletion) in the postsynaptic neurons. Furthermore, LTD was dependent on the activity of ryanodine receptors, and LTP was enhanced if postsynaptic ryanodine receptors were blocked by ryanodine. Not only was modification of the stimulated synapse dependent on the levels and source of postsynaptic calcium, but synaptic modification in adjacent synapses (heterosynaptic) was also affected. The authors propose that high levels of postsynaptic calcium lead to LTP but have no effect on heterosynapses because of inactivation of IP₃Rs. They further suggest that modest increases in intracellular calcium produce LTD, which can spread to heterosynaptic areas as long-range waves produced by activated IP₃Rs.

Nishiyama, M., Hong, K., Mikoshiba, K., Poo, M.-m., and Kato, K. (2000) Calcium stores regulate the polarity and input specificity of synaptic modification. Nature 408: 584-588. [Online Journal]