Formation and Retrieval of Associative Memory for a Complex Signal in Mice: Specific Involvement of Hippocampal Field CA1 Neurons

Most important events in the environment are complex in sensory terms. Integration of multimodal information relating to such complex signals by the brain is regarded by many investigators as a biological function of very early forms of consciousness. We report here use of a model of associative learning in mice in which electrocutaneous stimulation was combined with a complex conditioned signal consisting of simultaneous presentation of light and sound stimuli. These studies showed that mice successfully learned and formed long-term memory in a task consisting of conditioned reflex freezing in response to a complex conditioned stimulus. Immunohistochemical mapping of the neuronal expression of the c-fos gene in the hippocampus and associative retrosplenial cortex was performed to study the neural substrates of this memory. We found that only hippocampal field CA1 and not other areas of the hippocampus or the retrosplenial cortex underwent activation on retrieval of the associative memory for the complex conditioned signal, while its components produced no hippocampal activation. In addition, field CA1 showed a strong positive correlation between the level of freezing on retrieval of the memory and the number of neurons activated by retrieval of the memory. Thus, it can be suggested that hippocampal field CA1 is specifically involved in forming and retrieving associative memory for complex signals in the natural environment.