Frontal Association Cortex Is Engaged in Stimulus Integration during Associative Learning

• Published in: Current biology 2015-01, Vol.25 (1), p.117-123
• Main Authors: Nakayama, Daisuke, Baraki, Zohal, Onoue, Kousuke, Ikegaya, Yuji, Matsuki, Norio, Nomura, Hiroshi
• Format: Article
• Language: English
• Subjects: Animals; Association Learning - physiology; Conditioning (Psychology) - physiology; Fear - physiology; Frontal Lobe - physiology; Male; Mice, Inbred C57BL; Neurons - physiology; Protein Biosynthesis
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2014.10.078

The frontal association cortex (FrA) is implicated in higher brain function [1]. Aberrant FrA activity is likely to be involved in dementia pathology [2–4]. However, the functional circuits both within the FrA and with other regions are unclear. A recent study showed that inactivation of the FrA impairs memory consolidation of an auditory fear conditioning in young mice [5]. In addition, dendritic spine remodeling of FrA neurons is sensitive to paired sensory stimuli that produce associative memory [5]. These findings suggest that the FrA is engaged in neural processes critical to associative learning. Here we characterize stimulus integration in the mouse FrA during associative learning. We experimentally separated contextual fear conditioning into context exposure and shock, and found that memory formation requires protein synthesis associated with both context exposure and shock in the FrA. Both context exposure and shock trigger Arc, an activity-dependent immediate-early gene, expression in the FrA, and a subset of FrA neurons was dually activated by both stimuli. In addition, we found that the FrA receives projections from the perirhinal (PRh) and insular (IC) cortices and basolateral amygdala (BLA), which are implicated in context and shock encoding [6–8]. PRh and IC neurons projecting to the FrA were activated by context exposure and shock, respectively. Arc expression in the FrA associated with context exposure and shock depended on PRh activity and both IC and BLA activities, respectively. These findings indicate that the FrA is engaged in stimulus integration and contributes to memory formation in associative learning. •Protein synthesis in the FrA is required for encoding both context and shock•FrA receives convergent information regarding context and shock during fear learning•FrA neurons receive contextual information from the PRh•FrA neurons receive shock information from the IC and BLA Using a combination of large-scale brain activity imaging and pharmacological manipulation, Nakayama et al. find a novel role of the frontal association cortex (FrA) in associative learning. Their results demonstrate that the mouse FrA integrates sensory stimuli and encodes their association for a subsequent behavior.