Cholecystokinin enables neural plasticity in the auditory cortex

Patients with damage to the medial temporal lobe have great difficulty forming new long-term declarative memories, but still recall their remote memories suggesting remote memories are stored in the neocortex and the hippocampal system is necessary in neocortical memory encoding. In previous studies, we found that cortical projection neurons in the perirhinal/entorhinal cortices, the gateway of the hippicampal system to the neocortex, were mostly cholecystokinin (CCK) immunopositive. In the first experiment, local application of CCK in the auditory cortex of an anesthetized rat enabled a plastic change that caused a cortical neuron to start responding to a certain auditory stimulus after pairing this stimulus with the neuron’s best frequency tone for triggering action potentials. In the second experiment, the CCK application also enabled the auditory neuron to respond to a light stimulus after the light stimulus was paired with a noise-burst. In the third experiment, an application of a CCK receptor antagonist in the auditory cortex prevented the formation of the visuoauditory associative memory by classical conditioning, otherwise easily formed, in behaving rats. We conclude that the hippocampal system exerts its influence on cortical neuroplasticity through the action of CCK. CCK reinforces memory writing in the neocortex.