Psilocybin is a naturally occurring psychedelic compound with profound perception-, emotion- and cognition-altering properties. It has been hailed as a “breakthrough therapy” for pervasive, difficult-to-treat neuropsychiatric conditions, particularly major depressive disorder. As such, psilocybin has unique potential to treat the causes of psychiatric illness and enable recovery (1). However, the mechanisms by which psilocybin impacts brain function remain poorly understood.
Human studies using non-invasive fMRI brain imaging highlight psilocybin’s effect on regions associated with the default-mode network (DMN), particularly the prefrontal cortex (PFC) and hippocampus, as likely playing a key role in its consciousness-altering properties. Psilocybin may act to increase the variety of neural states by causing temporary reorganization of how brain regions interact, thereby, enabling the formation of new, long-range communication patterns (1, 2). This, in turn, may lead to more flexible cognition and emotional breakthroughs (3) via disruption of the excessive rumination and self-blaming seen in depression due to dominance of brain states by hyperactive PFC ‘top down’ control. This aligns well with the “relaxed beliefs under psychedelics (REBUS)” hypothesis (4), which claims that psychedelics decrease the influence of prior beliefs and expectations by decreasing cortical top-down inhibition. Such an effect may break the maladaptive thinking patterns in depression by enhancing bottom-up information transmission, allowing the emergence of a new, potentially brighter, perspective. However, it is difficult to investigate this hypothesis via indirect measures of brain activity such as fMRI; thus, invasive approaches to record the activity of neurons directly are required in rodents.
To reveal the neural and synaptic effects of psilocybin the student will record from multiple regions of the rodent brain during drug challenge. This will be facilitated by our ongoing collaboration with COMPASS Pathways UK, who are developing psilocybin for clinical use. Recordings will target DMN regions including PFC, parietal cortex, hippocampus and amygdala as well as early stages of the visual system such as LGN. Recordings in freely moving animals will determine psilocybin’s effect on motor, sensory and cognitive functions. Information theoretic analyses (5) on these large datasets will reveal drug-induced changes in the strength and direction of functional connectivity between recorded regions. The effect of psilocybin to induce protein and epigenetic changes will be determined post hoc. To translate these findings to the clinic the student will also carry out fMRI and magnetic resonance spectroscopy (MRS) recording in rodents under psilocybin challenge to correlate their invasive, direct measures of targeted regions with indirect but clinically relevant measures of global brain function and neurochemistry.
https://www.research.manchester.ac.uk/portal/j.gigg.html
https://www.research.manchester.ac.uk/portal/riccardo.storchi.html
https://www.research.manchester.ac.uk/portal/caroline.lea-carnall.html
https://www.mmu.ac.uk/life-sciences/staff/profile/index.php?id=2349
Entry Requirements
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.
How to Apply
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships
Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
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