Bdnf deletion or TrkB impairment in amygdala inhibits both appetitive and aversive learning

• Type of Material: Article
• Authors: Scott A. Heldt, University of Tennessee; Kelsey Zimmermann, Emory University; Kathryn Parker, Emory University; Meriem Gaval, Emory University; Kerry Ressler, Emory University
• Language: English
• Date: 2014-02-14
• Publisher: Society for Neuroscience
• Publication Version: Final Published Version
• Copyright Statement: © 2014 the authors.
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.4085-12.2014
• Title of Journal or Parent Work: Journal of Neuroscience
• ISSN: 0270-6474
• Volume: 34
• Issue: 7
• Start Page: 2444
• End Page: 2450
• Grant/Funding Information: This work was supported by National Institutes of Health Grants R01DA01962 and RC1MH088467, the Center for Behavioral Neuroscience (National Science Foundation agreement IBN-987675), the Burroughs Wellcome Fund, and a National Institutes of Health/National Center for Research Resources base Grant P51RR000165 to Yerkes National Primate Research Center.
• Keywords: Memory; Mice, Mutant Strains; BDNF; Brain-Derived Neurotrophic Factor; Signal Transduction; Mice; TrkB; learning; Receptor, trkB; Mice, Inbred C57BL; Association Learning; Appetite; Amygdala; Mice, Inbred BALB C; amygdala; Animals
• Research Categories: Psychology, Behavioral; Psychology, Experimental; Psychology, General

Abstract

Brain-derived neurotrophic factor (BDNF) is known to have an integral role in establishing stable memories after learning events. The neuroplasticity induced by Pavlovian fear conditioning has likewise been shown to rely on interactions between BDNF and its principal receptor, tyrosine kinase receptor B (TrkB), in the amygdala after training. Although the necessity of amygdala bdnf expression and TrkB activation for associative learning within aversive contexts has been explored, it is unclear to what extent this interaction is involved in appetitive learning. It is also unclear whether the noted increases in amygdala BDNF after fear conditioning are due to local gene transcription and translation or anterograde transmission from cortical regions. To address both of these questions, we used two lentiviral approaches in mice, using both fear conditioning and cocaine-conditioned place preference (CPP), during acquisition and extinction. First, we decreased expression of bdnf mRNA in the amygdala of homozygous floxed mice with a Cre-expressing virus. In a second set of studies, we infused a virus that expressed a dominant-negative TrkB isoform into the same region. These approaches significantly impaired consolidation of fear conditioning and cocaine-CPP, as well as extinction of CPP. Together, these data suggest that BDNF-TrkB signaling is critical for amygdala-dependent learning of both appetitive and aversive emotional memories.