CREB Regulates Memory Allocation in the Insular Cortex

• DOI: 10.1016/j.cub.2014.10.018
• Publication Date: 2014-11-17T01:13:08Z
• Authors: Yoshitake Sano; Justin L. Shobe; Miou Zhou; Shan Huang; Tristan Shuman; Denise J. Cai; Peyman Golshani; Masakazu Kamata; Alcino J. Silva
• Keywords: 0301 basic medicine; Biomedical and clinical sciences; 1.1 Normal biological development and functioning; Biological Psychology; Conditioning, Classical; Inbred C57BL; Basic Behavioral and Social Science; Medical and Health Sciences; Fluorescence; Mice; 03 medical and health sciences; Underpinning research; Memory; Behavioral and Social Science; Avoidance Learning; Psychology; Animals; Humans; Gene Silencing; Dental/Oral and Craniofacial Disease; Cyclic AMP Response Element-Binding Protein; In Situ Hybridization; In Situ Hybridization, Fluorescence; Cerebral Cortex; Neurons; Biomedical and Clinical Sciences; Agricultural and Biological Sciences(all); Biochemistry, Genetics and Molecular Biology(all); Psychology and Cognitive Sciences; Neurosciences; Pharmacology and Pharmaceutical Sciences; Biological Sciences; Classical; Mice, Inbred C57BL; Biological sciences; Mental Health; Taste; Neurological; Lithium Chloride; Conditioning; Developmental Biology

The molecular and cellular mechanisms of memory storage have attracted a great deal of attention. By comparison, little is known about memory allocation, the process that determines which specific neurons in a neural network will store a given memory. Previous studies demonstrated that memory allocation is not random in the amygdala; these studies showed that amygdala neurons with higher levels of the cyclic-AMP-response-element-binding protein (CREB) are more likely to be recruited into encoding and storing fear memory. To determine whether specific mechanisms also regulate memory allocation in other brain regions and whether CREB also has a role in this process, we studied insular cortical memory representations for conditioned taste aversion (CTA). In this task, an animal learns to associate a taste (conditioned stimulus [CS]) with the experience of malaise (such as that induced by LiCl; unconditioned stimulus [US]). The insular cortex is required for CTA memory formation and retrieval. CTA learning activates a subpopulation of neurons in this structure, and the insular cortex and the basolateral amygdala (BLA) interact during CTA formation. Here, we used a combination of approaches, including viral vector transfections of insular cortex, arc fluorescence in situ hybridization (FISH), and designer receptors exclusively activated by designer drugs (DREADD) system, to show that CREB levels determine which insular cortical neurons go on to encode a given conditioned taste memory.