Does Associative LTP Underlie Classical Conditioning?

A major goal in cognitive neuroscience is to identify the cellular substrates that underlie learning and memory. One prominent approach toward achieving this goal has been to study the enhancement of synaptic transmission produced by high-frequency electrical stimulation. This activity-dependent increase in synaptic strength, which shares characteristics with memory, is commonly referred to as long-term potentiation (LTP). One focus within the LTP field is a phenomenon termed “associative LTP.” Associative LTP is an enhancement of response that develops specifically as a result of the coactivation of two anatomically distinct inputs. Some investigators have suggested that associative LTP is a substrate for classical conditioning, based on the apparent correspondence between the parameters of electrical stimulation used to induce associative LTP and the parameters of training used in classical conditioning. This commentary presents our view that the notion of a putative associative LTP/classical conditioning connection is of limited heuristic value. We have proposed an alternative interpretation of the findings based on the hypothesis that an associative LTP-like process occurs during behavioral conditions that produce intense coactivation of different groups of hippocampal synapses. Endogenous associative LTP might occur as a result of the synchronous activation of the hippocampus by rhythmic bursting activity (theta rhythm) and afferent activity conveying information about the animal’s environment. This approach minimizes fitting models of learning to the temporal constraints of classical conditioning training parameters and emphasizes an understanding of the behavioral conditions that maximize synaptic plasticity and information storage