2018 — 2019 |
Burghardt, Nesha Star Likhtik, Ekaterina (co-PI) [⬀] |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Circuit-Level Regulation of Fear and Safety Learning in Chronically Stressed Mice
Project Summary/Abstract It has long been recognized that chronic exposure to stressful adverse life experiences confers susceptibility to developing post-traumatic stress disorder (PTSD), a stressor and trauma-related disorder characterized by intense fearful memory formation. Many of the long-lasting symptoms associated with PTSD can be attributed to an impaired ability to discriminate between cues associated with threat from those associated with safety. Chronic stress is believed to play a key role in the etiology of PTSD by altering the brain's fear memory system in a way that increases generalization of fear to `safe' cues that are unrelated to the trauma. Recent findings have suggested that memories of fear and safety are encoded and expressed via an elaborate pattern of communication between the medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA), with BLA activity being suppressed by input from the mPFC during periods of recognized safety. Moreover, evidence suggests that basal forebrain (BF) cholinergic inputs to the mPFC play a critical role in facilitating the detection and encoding of certain types of learned cues. It remains unknown, however, whether cholinergic input to the mPFC is involved in the encoding of safety cues, and no studies have conducted a circuit-level analysis to examine how a history of chronic stress regulates dynamic network activity between the BF, mPFC and BLA. In the present proposal, we will first use behavioral and immunocytochemical techniques to characterize the effects of chronic stress on fear and safety discrimination and activity within the basal forebrain cholinergic system in male and female mice (Aim I). Next, we will use multisite neurophysiological recordings in awake-behaving male and female mice to systematically examine how a history of chronic stress regulates dynamic patterns of neural activity between the BF, mPFC and BLA during fear and safety discrimination (Aim II). Finally, we will use optogenetic methods to manipulate activity in the BF-mPFC pathway to determine how cholinergic input contributes to fear discrimination learning and how it might be impacted by a history of chronic stress in both sexes (Aim III). Our findings have the potential to significantly broaden our current understanding of how exposure to chronic stress modulates fear discrimination and the adaptive use of safety cues at the neural circuit level, findings which may have relevance for the treatment of disorders such as PTSD.
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0.904 |
2019 — 2021 |
Burghardt, Nesha Star Schafe, Glenn E |
R25Activity Code Description: For support to develop and/or implement a program as it relates to a category in one or more of the areas of education, information, training, technical assistance, coordination, or evaluation. |
Bp-Endure At Hunter and Nyu
? DESCRIPTION (provided by applicant): Diverse racial and ethnic groups, as well as individuals with disabilities and/or having socially, economically, or educationally disadvantaged backgrounds are underrepresented in neuroscience. Hunter College of the City University of New York (CUNY) and New York University (NYU) recognize that increasing the number of highly qualified neuroscientists from these underrepresented populations is integral to our future as academic and research institutions. Hunter College and NYU aim to increase the number of well-trained, diverse neuroscientists. BP-ENDURE at Hunter and NYU proposes to capitalize on and expand on the objectives and success of our first 5 years of BP-ENDURE funding, which has produced 15 program graduates in the program's first 4 years who have applied to and been offered admission to graduate school. Importantly, 100% of BP-ENDURE graduates from Hunter and NYU who have applied to doctoral programs were accepted. Some are at the best universities in the country, such as Harvard, Columbia, Johns Hopkins, UC Berkeley, Brown, and Yale. The overall goal of this application is to develop a neuroscience training program at Hunter that will encourage and prepare students from diverse backgrounds to enter into and succeed in neuroscience PhD programs. To achieve this goal, Hunter College has developed a research-educational partnership with four outstanding T32-awarded universities-New York University, Brown University, University of Michigan, and Vanderbilt University. This partnership will expose 12 BP-ENDURE-trainee students per year to a research-intensive curriculum and an environment of excellence and active research. Moreover, because of the diversity of the proposed mentors, students will be exposed to a broad spectrum of researchers, including basic neuroscientists interested in central nervous system (CNS) issues and applied neuroscientists from the areas of clinical, social, health, developmental, computational, and cognitive neuropsychology. During this funding period, four developmental activities are proposed: (1) To develop an outstanding group of undergraduate students with diverse backgrounds dedicated to neuroscience research; (2) To provide scientific skills and research experiences to our trainees through research placement with actively funded neuroscientists in three different university settings, so as to expose students to laboratories that differ in scale, hierarchically, stylisticaly, and geographically; (3) To develop academic development and curriculum enhancement activities rooted in the student's research activities; and (4) To maintain an effective Administrative Core to support our students' needs and development. Our measurable objectives during the requested funding period include: (1) attaining 85 to 90% acceptance of trainees to graduate school programs in neuroscience; (2) improving our students' quantitative skills and academic achievements, as well as their (3) scientific writing (of research and grants) and oral presentation skills. Outcome from evaluations of the Steering Committee, the external evaluator, and the Administrative Core will guide future modifications to our training initiatives.
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0.904 |