Psychedelic drugs and serotonergic modulation of functional connectivity in neuronal microcircuits

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 by different societies 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 psychedelic compounds, exerted primarily by activation of serotonergic 5HT-2A receptors, and related drugs.

Our aim 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., Cell Reports 2023). Towards this end, we will use high-density multi-electrode arrays (Steinmetz et al., Science 2021), imaging and advanced computational methods to record and analyse spontaneous and sensory evoked activity of large neuronal populations in mice. 

There is a scope to tailor the specific research questions to your interests and strengths. In particular, the research can have a stronger emphasis either on the experimental or the computational research components. The former is typically more appropriate if your background is in biology, neuroscience, pharmacology, medicine or psychology, while the latter is particularly suitable if you have a background in programming or quantitative subjects, e.g., mathematics, statistics, physics or computer science and engineering. The decision on your second/third supervisor(s) will also be based on the specific research questions that we decide to explore.

You 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.

Please feel free to get in touch with the PI for any further information or informal inquiries (michael.okun@nottingham.ac.uk).