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  Psychedelic drugs and serotonergic modulation of functional connectivity in cortical microcircuits


   Department of Psychology

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  Dr Michael Okun  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Psychoactive drugs result in profound alterations of our state of consciousness. Well known examples of such drugs are general anaesthetics, in use since mid-19th century, and psychedelics, which are consumed from times immemorial. The way these drugs operate is far from understood, although last decades witnessed a significant progress on this question. Most of the research has focused on the cellular mechanisms of action of such drugs in the central nervous system, elucidating the receptors and intracellular molecular pathways that are involved. However, knowing how a neuron is affected when considered in isolation (typically in an in vitro preparation), does not explain how the drug affects the intact brain, where neurons are highly interconnected.

The aim of the present project is to further the systems level understanding of the changes in cortical activity under the effect of classical hallucinogens, exerted primarily by activation of serotonergic 5HT-2A receptors. Our specific objective is to determine the changes in spontaneous and sensory evoked activity produced by 5-HT2A agonists at the level of single neurons and neuronal populations in sensory and frontal cortex (Dearnley et al., 2021). Towards this end, we will use high-density multi-electrode arrays (Steinmetz et al., 2021), imaging (Lee et al. 2020) and advanced computational methods to record and analyse spontaneous and sensory-evoked activity of large neuronal populations in mice.

The PhD student will gain expertise in cutting-edge methods in systems and computational neuroscience and will help advancing our understanding of a fundamental question at the intersection of neuropharmacology and systems neuroscience.

Entry requirements

Essential: at least a 2:1 (or equivalent) undergraduate degree in neuroscience or related subject or in exact sciences (e.g., mathematics, physics, computer science, data science), good written and oral communication skills. MSc level qualification or commensurate relevant research methods experience, programming experience

Biological Sciences (4) Computer Science (8) Mathematics (25) Physics (29) Psychology (31)

Funding Notes

Self funded or externally sponsored students only. Intakes are usually
October and March annually.
The University has some scholarships under competition each year. More
details can be found at
https://www.sheffield.ac.uk/postgraduate/phd/scholarships

References

Dearnley B, Dervinis M, Shaw M, Okun M (2021) Stretching and squeezing of neuronal log firing rate distribution by psychedelic and intrinsic brain state transitions. bioRxiv:2021.08.22.457198
Lee L et al. (2020) Key Aspects of Neurovascular Control Mediated by Specific Populations of Inhibitory Cortical Interneurons. Cerebral Cortex 30(4), 2452–2464
Steinmetz NA et al. (2021) Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings. Science 372, eabf4588

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