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The Role of Forebrain Neuropeptide Y in the Regulation and Development of PTSD-like Behaviors

Schmeltzer, Sarah N
http://orcid.org/0000-0003-4333-1566
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1479820132199223

Abstract Details

2016, PhD, University of Cincinnati, Medicine: Neuroscience/Medical Science Scholars Interdisciplinary.
Posttraumatic Stress Disorder (PTSD) is a debilitating psychiatric syndrome evoked by trauma. Underlying mechanisms and neurobiological factors contributing to PTSD pathophysiology are still being understood. Recent studies implicate Neuropeptide Y (NPY), a 36-amino acid peptide transmitter. NPY is highly expressed in forebrain regions of the amygdala, prefrontal cortex and hippocampus, which show dysregulation in PTSD. In previous studies, we reported reduced CSF NPY levels in veterans with combat-PTSD compared to healthy volunteers and combat exposed veterans (Sah et al., 2009, 2014). Polymorphisms in the NPY gene are associated with stress susceptibility and coping. Investigating how NPY contributes to PTSD pathophysiology could lead to a better understanding of the disorder, and identify potential therapeutic and diagnostic markers for PTSD. This dissertation investigates contributions of forebrain NPY to PTSD relevant behaviors using rodent models. Studies primarily focused on the medial prefrontal cortex (mPFC) and the amygdala, regions reported to malfunction in individuals with PTSD. Using pharmacological interventions, significant effects of infralimbic (IL) NPY were observed on extinction consolidation and retrieval of extinction. Functional modulation of excitatory-inhibitory neurotransmission and localization of NPY Y1 receptor on IL projection neurons revealed a pathway by which elevated IL-PFC NPY may modulate fear memory. Using tract-tracing studies, a novel NPY efferent pathway from the raphe nucleus to the IL cortex was identified. Since raphe-IL pathways are reportedly recruited in behaviors resulting from uncontrollable stress situations, this NPY circuit is particularly relevant to PTSD, a disorder stemming mostly from uncontrollable trauma.
Stephen Benoit, Ph.D. (Committee Chair)
James Herman, Ph.D. (Committee Member)
Renu Sah, Ph.D. (Committee Member)
Kim Seroogy, Ph.D. (Committee Member)
Matia Solomon, Ph.D. (Committee Member)
220 p.
Neurology
PTSD; Post-traumatic stress; Neuropeptide Y; NPY; fear; fear conditioning

Recommended Citations

Citations

  • Schmeltzer, S. N. (2016). The Role of Forebrain Neuropeptide Y in the Regulation and Development of PTSD-like Behaviors [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1479820132199223

    APA Style (7th edition)

  • Schmeltzer, Sarah. The Role of Forebrain Neuropeptide Y in the Regulation and Development of PTSD-like Behaviors. 2016. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1479820132199223.

    MLA Style (8th edition)

  • Schmeltzer, Sarah. "The Role of Forebrain Neuropeptide Y in the Regulation and Development of PTSD-like Behaviors." Doctoral dissertation, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1479820132199223

    Chicago Manual of Style (17th edition)

ucin1479820132199223
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This open access ETD is published by University of Cincinnati and OhioLINK.