Background: Alzheimer’s disease (AD) is an incurable and debilitating neurodegenerative disease characterized by a progressive loss of cognitive and bodily functions. The disease is associated with accumulation of toxic peptides and cholinergic degeneration in the brain. Event-related potentials (ERPs) are measured by electroencephalography (EEG) and have been widely studied in AD patients, since ERPs represent an objective measure of brain processing. The P300 ERP is of particular interest because a compromised P300 is commonly associated with the loss of cognitive function in AD. A rodent model of P300 would be useful in developing new pharmacological compounds that affect the cognitive system.
Methods: ERPs were recorded by EEG from hippocampus, auditory cortex, parietal cortex, and frontal/prelimbic cortex during an auditory discrimination paradigm in rats. Three experiments were conducted using two different experimental setups. A total of three sessions were analyzed. 1: Sensory paradigm with no discrimination of tones, 2: discrimination paradigm, and 3: scopolamine (0.1mg/kg) / saline treated rats in the discrimination paradigm for each experiment.
Results: No P300 could be identified during experiment 1 (Three tone discrimination). A clearly defined P300 developed in hippocampus in experiment 2+3 and prelimbic cortex in experiment 3 with a latency of 170-180ms during discrimination training of the rats in experiment 2 and 3 (Two tone discrimination). Scopolamine increased latency in hippocampus in experiment 2 similar to what is seen in humans providing evidence that the P300 observed in the rats are translatable to the P300 seen in humans.
Conclusion: A method to evoke a P300 in rats was established. The P300 identified in rat hippocampus shows similar features to the human P300 and would be useful in studying new compounds that affect the cognitive function in AD. The prelimbic cortex also showed a trend towards mimicking human P300 but further studies are required to validate this.