Learning-induced enduring changes in functional connectivity among prefrontal cortical neurons.

Current thinking about how memories are stored in the brain has been profoundly influenced by Donald O. Hebb's cell assembly hypothesis, which posits that (1) learning produces a stable alteration in patterns of connectivity among repeatedly coactivated neurons, and (2) memory retrieval involves reactivation of those altered patterns of connectivity. However, learning-induced changes in connectivity that persist over long periods of time have not been clearly demonstrated. In the present study, two spatial navigation tasks and a long-term ensemble recording technique are used to describe long-lasting modifications in functional connectivity (FC) (defined as changes in synchronous firing) of prefrontal cortical neurons in behaving rats. Animals were initially trained to alternate visiting two spatial locations on a figure-8-shaped maze to obtain a reward (alternating task 1). Afterward, while continuing on task 1, animals were additionally trained to visit only one spatial location on the same maze to obtain a reward (unilateral task 2). Multiple single units were recorded while rats were undergoing acquisition, retention, and performance of both tasks. Our data indicate that correlated firing of prefrontal cortical neurons changed significantly in early phases of training when learning rate was maximal but became progressively smaller in later phases when learning reached asymptote. After animals became proficient, FC remained constant, although neuronal activities varied across two different tasks. The present finding of negatively accelerated changes in FC confirms associative learning theories and provides crucial neurophysiological evidence for Hebb's hypothesis.