Is contiguity detection in classical conditioning a system or a cellular property? Learning in Aplysia suggests a possible molecular site

It is shown that effective activation of the NMDA-gated Ca 2+ conductance requires temporal pairing of two signals: transmitter binding and postsynaptic depolarization, which could also contribute to the learning of predictive relationships.

Abstract

The nervous systems of a broad variety of animals have evolved the ability to recognize predictive relationships between events if these occur repeatedly in a temporally contiguous manner. Recent evidence suggests that, in the simplest cases, learning about these predictive relationships, such as occurs during conditioning, may be mediated by molecular interactions within individual nerve cells. Studies of conditioning in both Aplysia and Drosophila indicate that the enzyme adenylate cyclase may serve as a molecular site of convergence between two signals: Ca2+ influx, the signal from the conditioned stimulus, and transmitter, the signal from the unconditioned stimulus. We review recent evidence that this dually regulated enzyme may have the necessary properties for it to play such an associative role. Recent analyses of associative LTP in the hippocampus reveal a second molecular mechanism for associative synaptic plasticity, which could also contribute to the learning of predictive relationships. In a fashion analogous to the dual regulation of adenylate cyclase, effective activation of the NMDA-gated Ca2+ conductance requires temporal pairing of two signals: transmitter binding and postsynaptic depolarization.