Role of Dorsal Hippocampal Muscarinic Receptor Activity in Acquisition and Retention of Single- Versus Multiple-Trial Contextual Fear Conditioning in Adolescent Rats

The present study examined the effects of the muscarinic acetylcholine receptor (mAChR) antagonist, scopolamine, on standard contextual fear conditioning (sCFC). It compared effects of the drug on acquisition (post-shock freezing) versus 24-hr retention of a context-shock association acquired after one or three pairings of a context with unsignaled shock. During single-trial sCFC, systemic scopolamine (0.5 mg/kg, i.p.) prior to training abolished both post-shock and retention freezing (Experiment 1). This same injection during multiple-trial sCFC also abolished post-shock freezing and impaired 24-hr retention freezing (Experiment 2). These results indicate that cholinergic signaling mediates both acquisition and 24-hr retention of a context-shock association across different trial parameters. Experiment 3 further explored these effects by infusing scopolamine (35 mu g per side) into the dorsal hippocampus (dHPC) prior to training in single versus multiple-trial sCFC. This infusion spared post-shock but abolished retention test freezing in single-trial sCFC (Experiment 3A), and had no effect on multiple-trial sCFC (Experiment 3B). The current findings suggest that brain-wide cholinergic signaling mediates acquisition and retention of single-trial sCFC. Despite this, while muscarinic cholinergic signaling in the dHPC does mediate retention of single-trial sCFC, it is not required for acquisition of either variant, or retention of multiple-trial sCFC. These findings also rule out impaired sensory processing of contextual cues as a mechanism of impaired context learning by dHPC scopolamine. The results are discussed in relation to the role of cholinergic function across multiple brain memory systems in elemental versus configural forms of contextual fear conditioning (Fanselow, 2010; Rudy, 2009).