A switching role of postsynaptic calcium in the induction of long-term potentiation or long-term depression in visual cortex

Abstract

Long-term potentiation (LTP) and depression (LTD) are considered to be an initial step in processes governing experience-dependent changes in neuronal function in cerebral neocortex. As a mechanism for the induction of LTP and LTD, it is hypothesized that an input-associated rise of Ca²⁺beyond a certain threshold at postsynaptic sites leads to LTP while a lower rise below the threshold leads to LTD. To test this Ca²⁺-switching hypothesis, the method of microscopic fluorometry with Ca²⁺indicators such as fura-2 has been employed. In this review, problems with this fura-2 method are described, and results obtained with other indicators having weaker Ca²⁺-chelating action are mentioned briefly. Experimental results indicating the involvement of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and protein phosphatase (calcineurin) are also reviewed, and a model that includes the spatiotemporal dynamics of Ca²⁺and the intracellular location of both enzymes as variables is proposed as a modification of the Ca²⁺-switching hypothesis.