This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Understanding the cellular mechanisms mediating emotional regulation ?both aversive and appetitive - is of critical importance for a variety of psychiatric disorders, such as Posttraumatic Stress Disorder (PTSD) and Drug Abuse. Through a combination of anatomical, behavioral, molecular, and genetic techniques, our experiments have the potential to resolve an outstanding issue in the role of Brain Derived Neurotrophic Factor ?a peptide known to be involved in emotional regulation- within the Prefrontal Cortex in modulating expression of appetitive and aversive memories, and extinction of those memories. We have made considerable progress on all Specific Aims in the 2009-2010 funding period. In a recent publication (Choi et al., 2010, PNAS), we demonstrated that BDNF within the prelimbic prefrontal cortex modulated amygdala-dependent expression of fear learning. We are following these experiments up with further studies now examining the role of similar manipulations in the acquisition and expression of appetitive, conditioned place preference behavior. We also showed that a small molecule BDNF ?TrkB agonist, 7,8-DHF, acts as a systemic agonist at the TrkB receptor to enhance emotional memory and to reverse deficits from the prelimbic bdnf knockout mouse. Additional studies are ongoing to determine exactly which neuronal cell types within the prefrontal cortex are responsible for these BDNF-TrkB mediated effects.
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