Concurrent modulation of anxiety and memory in the infralimbic ventromedial prefrontal cortex.

Abstract

The present series of experiments systematically investigated the relative contributions of the infralimbic area of the orbitomedial prefrontal cortex to the concurrent modulation of anxiety-like behaviour, aversive learning and active working memory in CD-1 mice. Overlapping neural transmission was evaluated by testing the possibility that the behavioural effects of kappa opioid or muscarinic M1 drug infusions in the infralimbic orbitomedial prefrontal cortex could concurrently influence both cognitive/behavioural processes. The behavioural results derived from Experiments 2a, 2b, 3, 4a, 4b, 4c and 5 provide direct evidence for orbitomedial prefrontal cortical involvement in the concurrent modulation of anxiety and associative working memory. In addition, the aggregate results support the hypotheses that (a) cholinergic muscarinic M1 receptor activation in the infralimbic cortex enhances anxiety, aversive learning and active working memory, (b) kappa opioid receptor activation in the infralimbic cortex reduces anxiety, disrupts aversive learning and enhances active working memory, (c) kappa opioid and muscarinic M1 receptors interact in the infralimbic cortex in the concurrent modulation of anxiety and memory, and (d) basal forebrain-orbitomedial prefrontal cholinergic terminal activation likely influences anxiety and working memory in the orbitomedial prefrontal cortex through effects on attentional processing. Results are discussed in light of theoretical perspectives that view anxiety disorders in the cognitive, rather than the emotional domain. We think our systematic approach to the investigation of the role of the orbitomedial prefrontal cortex in the concurrent modulation of anxiety, working memory and attentional processing, is contributing to the understanding of the complex nature of orbitomedial prefrontal neural circuitry and the complex executive functions subserved by this associative cortical network.