Abstract

This experiment investigates the role of the orbitofrontal cortex (OFC) in facilitating integral representation of an auditory space. To test rats’ ability to learn holistic stimulus dimensions, we trained 20 rats on a Pavlovian task in which 2 sets of auditory cues were configured to represent a 2-dimensional space. The stimuli consisted of 12 distinct tone frequencies and 12 distinct clicker
frequencies, which were combined for 144 compound auditory stimuli. 2 of the auditory compound cues were paired with a saccharin reward. We sought to determine whether temporary DREADD induced inactivation of the OFC across the learning phase of the task would impair learning between the compound stimuli and saccharin. We injected AAV8-CaMKIIa-hM4Di-mCherry
(n=11) or AAV8-CaMKIIa-mCherry (n=9) into the OFC prior to the experiment. To learn the stimulus set, rats were exposed to ‘random walk’ paths through the auditory space, such that they would listen to a progression of compound cues in which each transition consisted of an incremental change in frequency in one of the auditory dimensions. To assess the role of the OFC
in learning these compound cues, rats received injections of a DREADD agonist (Agonist 21) or saline throughout the first 16 days of the 34-day experiment. Learning was assessed through
reward anticipation and performance on 2 extinction tests (days 17 and 34). OFC-inactivation inhibited the ability of rats to respond in anticipation of the reward based on the particular compound cue configurations, indicating that OFC is required for integral learning in a reward setting.