2014 — 2018 |
Morrow, Jonathan David |
K08Activity Code Description: To provide the opportunity for promising medical scientists with demonstrated aptitude to develop into independent investigators, or for faculty members to pursue research aspects of categorical areas applicable to the awarding unit, and aid in filling the academic faculty gap in these shortage areas within health profession's institutions of the country. |
Neural Circuitry of Shared Vulnerability to Both Ptsd and Addiction
DESCRIPTION (provided by applicant): This K08 proposal describes a 5-year training program for the development of an academic career in addiction research. The candidate completed his M.D. and Ph.D. in Neuroscience, and then went on to complete a structured residency in Psychiatry at the University of Michigan. He was recently appointed Assistant Professor of Psychiatry at University of Michigan, where in addition to basic research he now treats patients with substance use disorders at the Addiction Treatment Services clinic. The candidate's education and training in both neuroscience and psychiatry have prepared him well for this project, and he will now expand on his scientific skills through a unique integration of interdepartmental resources. To achieve full research independence, he has identified three key Training Objectives: (1) to gain proficiency in advanced neuroanatomical techniques, particularly immunohistochemistry, (2) to gain expertise in microinjections and the use of viral vectors to experimentally manipulate behavior, and (3) to learn how to use optogenetics as a tool for interrogating neural circuits that influence specific behaviors. The proposed K08 project will take place within the Department of Psychiatry and the Molecular & Behavioral Neuroscience Institute at the University of Michigan. The Department and Institute benefit from close collaborative relationships with other units including Bioengineering, Psychology, Radiology, and the CTSA- funded Michigan Institute for Clinical and Health Research. This vigorous research environment includes ample access to behavioral testing facilities, histology and microscopy resources, and animal housing, and it nurtures an expanding group of translational psychiatric researchers. The primary mentor, Terry Robinson PhD, is a productive and well-funded neuroscientist who has more than 30 years of experience with basic addiction research, and an established track record of mentoring junior investigators. The candidate will also benefit from two local co-mentors, Stanley Watson MD PhD, who pioneered the use of immunohistochemistry to study emotional behavior and has mentored several successful physician-scientists over his 30+ years of research, and Gina Poe PhD, an Associate Professor of Anesthesiology who has expertise in the use of optogenetics to study behavior in rats. Pedro Lowenstein MD PhD is an experienced consultant on this project with considerable expertise in viral vectors and translational research. The research project focuses on identifying common neurobiological substrates that confer vulnerability both to addiction and to frequently co-occurring disorders such as post-traumatic stress disorder. This will be accomplished by identifying neural circuits responsible for generating excessive emotional and motivational responses to both appetitive and aversive conditioned cues. The specific aims include: 1) identifying areas of overlap in the neurons and circuits activated by both appetitive and aversive conditioned cues, 2) testing whether increasing connectivity within limbic circuitry can simultaneously reduce both conditioned approach and conditioned fear, and 3) using optogenetics to identify specific pathways that exert inhibitory control over both appetitive and aversive motivational responses. The proposed K08 project is well-aligned with the missions of the NIH and NIDA. The project will train a promising scientist and help clarify neurobiological pathways to addiction and frequently co-occurring disorders, which is a significant public health priority.
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2019 — 2021 |
Morrow, Jonathan David |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Individual Differences in Epigenetic Regulation of Emotional Learning @ University of Michigan At Ann Arbor
PROJECT SUMMARY/ABSTRACT This research project focuses on identifying common neurobiological substrates that confer vulnerability both to addiction and to frequently co-occurring disorders such as post-traumatic stress disorder (PTSD). Pavlovian conditioning procedures will be used to distinguish ?sign-tracking? rats that tend to attribute high levels of motivational significance to discrete predictive cues while largely ignoring context, from ?goal-tracking? rats that make more use of context to appropriately modify their emotional responses. Sign-tracking individuals are more prone to both addiction- and PTSD-like behaviors than goal-trackers. The neurobiological basis of these behavioral traits will be explored by testing for differences between sign- and goal-trackers in dynamic epigenetic histone acetylation, brain-derived neurotrophic factor (BDNF) expression, and functional connectivity within key limbic circuits known to mediate motivated behavior, namely the pathway from ventral hippocampus to medial prefrontal cortex to basolateral amygdala and nucleus accumbens. Epigenetic changes and growth factor expression will also be manipulated using viral vectors to test for a causal influence on conditioned motivational responses to appetitive and aversive cues and contexts, as well as electrophysiological measures of connectivity and synaptic efficiency within the limbic pathway of interest. These experiments will test the hypothesis that decreased histone acetylation in goal-trackers relative to sign- trackers after behavioral conditioning leads to increased transcription of BDNF, which in turn is transported axonally and released onto medial prefrontal cortical targets. The BDNF then causes an increase in synaptic connectivity between the medial prefrontal cortex and its downstream targets, the basolateral amygdala and nucleus accumbens. Thus, goal-trackers are hypothesized to have an increased capacity to use contextual information, derived from hippocampal inputs and relayed through the medial prefrontal cortex, to appropriately modify subcortical responses to cues associated with emotionally salient events. This proposed R01 project is well-aligned with the missions of the NIH and NIDA, as it will help clarify neurobiological pathways to addiction and frequently co-occurring disorders, which is a significant public health priority.
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