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The retrosplenial cortex (RSP) is highly interconnected with medial temporal lobe structures, yet relatively little is known about its specific contributions to learning and memory. One possibility is that RSP is involved in forming associations between multiple sensory stimuli. Indeed, damage to RSP disrupts learning about spatial or contextual cues and also impairs learning about co-occurring conditioned stimuli (CSs). Two experiments were conducted to test this notion more rigorously. In Experiment 1, rats were trained in a serial feature negative discrimination task consisting of reinforced presentations of a tone alone and nonreinforced serial presentations of a light followed by the tone. Thus, in contrast to prior studies, this paradigm involved serial presentation of conditioned stimuli (CS), rather than simultaneous presentation. Rats with damage to RSP failed to acquire the discrimination, indicating that RSP is required for forming associations between sensory stimuli regardless of whether they occur serially or simultaneously. In Experiment 2, a sensory preconditioning task was used to determine if RSP was necessary for forming associations between stimuli even in the absence of reinforcement. During the first phase of this procedure, one auditory stimulus was paired with a light while a second auditory stimulus was presented alone. In the next phase of training, the same light was paired with food. During the final phase of the procedure both auditory stimuli were presented alone during a single session. Control, but not RSP-lesioned rats, exhibited more food cup behavior following presentation of the auditory cue that was previously paired with light compared with the unpaired auditory stimulus, indicating that a stimulus-stimulus association was formed during the first phase of training. These results support the idea that RSP has a fundamental role in forming associations between environmental stimuli.

Involvement of retrosplenial cortex in forming associations between multiple sensory stimuli.