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Effect of psilocybin on persistent aversive signaling across the cingulate cortex Sophie Rogers
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Rogers, Sophie, author.
- Language:
- English
- Subjects (All):
- Neurosciences.
- Psychology.
- Medicine.
- Clinical psychology.
- 0317.
- 0621.
- 0564.
- 0622.
- Local Subjects:
- Neurosciences.
- Psychology.
- Medicine.
- Clinical psychology.
- 0317.
- 0621.
- 0564.
- 0622.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (307 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- Adaptive behavior depends on the brain's ability to predict and control aversive outcomes. Dysfunctions in this process underlie disorders of chronic pain and pathological fear. Recently, serotonergic psychedelics, such as psilocybin, have shown great promise towards resolving these disorders, but their mechanisms are unknown. The cingulate cortex, comprising the anterior cingulate cortex (ACC) and the retrosplenial cortex (RSC), mediates affective, mnemonic, and decision-related aspects of these experiences, yet how their computations are implemented and reorganized during perseverative fear and pain and by psychedelics remains unclear. This dissertation examines how the psychedelic psilocybin acutely and persistently alters cingulate dynamics to reverse fear and pain perseverance. Using longitudinal calcium imaging, I first show that the ACC and RSC exhibit distinct population dynamics during aversive learning. ACC ensembles stably encode pain and predict freezing decisions across days, whereas RSC ensembles gradually acquire and stabilize predictive codes for shock timing and omission, enabling fear extinction. Psilocybin enhances fear extinction by recruiting new RSC neurons that encode safety and omission, while silencing acquisition-dominant ensembles. More shock-predicting neurons are inhibited in mice with psilocybin-enhanced extinction, suggesting that psilocybin facilitates the rewriting of temporal predictions underlying fear. In a chronic pain model, I demonstrate that injury induces hyper-hierarchical ACC network organization, fracturing the population code for spontaneous behaviors and latent pain states. Psilocybin, but not morphine, acutely and persistently redistributes network dynamics, restores single-cell and ensemble coding of behavioral states, and reduces pain-directed behaviors-indicating a fundamentally distinct form of analgesia. Together, these findings reveal that psilocybin reorganizes regionally specialized computations across the cingulate cortex according to a shared principle of predictive control, renormalizing predictive (RSC) and policy (ACC) circuits to restore adaptive flexibility. This work supports the unification effects of psilocybin on locally distinct computations underlying fear extinction and pain relief under a common computational framework of cortical reconfiguration
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Corder, Gregory Committee members: Geffen, Maria; Heller, Elizabeth; Foster, Brett; Wallisch, Pascal
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247980506
- Access Restriction:
- Restricted for use by site license
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