Revealing the circuit mechanisms of altered conscious perception with neuropixels recordings and biophysically-inspired neural networks.

Psilocybin is a compound found in 'magic mushrooms' that alters conscious perception. Our goal is to understand how psilocybin changes brain connectivity and conscious perception. To achieve this, we will bring together experts in brain anatomy and function with experts in artificial intelligence. We will first analyse and combine data on the brain's anatomy and function. We will use this data to simulate the effects of psilocybin on the brain's circuits. We can then analyse the simulation to learn how psilocybin changes brain activity and the conscious experience.

Psilocybin has exploded in popularity as a recreational drug, a mental health treatment and an aid for creativity. The popularity derives in part from its effects on conscious perception. Conscious perception emerges from activity across scales of brain organisation. We aim to integrate across these scales. In this way, we will learn how the local effects of psilocybin lead to reorganisation of connections across the brain.

The nature of the psilocybin experience does not only depend on biological factors. The mental state of the person taking the drug also affects the experience. We need to know how mental states can change psilocybin's effects on neural circuits. This would show how psychological and biological factors influence each other and determine our experience. Both natural chemical transmitters and drugs bind with receptors to open channels in neurons, much as a key fits a lock to open a door. We recently found the receptors that psilocybin binds to in different amounts across different brain areas. We aim to test whether this can explain the powerful influence of psilocybin on conscious perception.

We propose to use a new advanced recording technology to measure psilocybin's effects on the activity of hundreds of neurons in the rat brain. We will combine this data with our maps
of the locations of receptors in the brain. We will use this data to build a simulation of psilocybin's effects on the brain based on real biology. This will provide a missing link between the psychological and biological effects of psilocybin. Scientists can use this to design and refine future experiments.

We have three key objectives:

1. To analyse recordings of neural activity from the rat brain to identify how psilocybin's changes brain architecture.
2. To simulate how the mental state can combine with biological factors and alter the psilocybin experience
3. To simulate how the brain's physiology and anatomy determine psilocybin's ability to alter conscious perception.

This project will create an open software platform to advance our understanding of psychedelic drugs. This has the potential to move forward both our fundamental understanding of the brain and drug development.

Psilocybin is a psychedelic drug that alters conscious perception. The goal of this project is to pinpoint the critical changes to neural circuit physiology that produce these alterations. We will achieve this by integrating anatomy, physiology and imaging data with neural network models of cognition.

Psilocybin has exploded in popularity as a recreational drug and a mental health treatment. However, relatively little is known about how psilocybin affects neural circuitry locally or across the cortex. The psilocybin experience is also affected by contextual factors such as cognitive state. We need to know how cognitive states modulate psilocybin's effects on neural circuit interactions. This would show how the psychological and pharmacological determinants of subjective experience interact. At the pharmacological level, psilocybin acts on the 5-HT1A and 5-HT2 receptors. We recently discovered that 5-HT1A and 5-HT2 receptors have contrasting expression across the cortex. We aim to test whether this can account for psilocybin's powerful influence on tasks of conscious perception.

We have three key objectives:
1. To analyse large-scale chronic neural recordings to identify how psilocybin's circuit-level effects change the functional network organisation across the rat frontal cortex.
2. To construct a biophysically-inspired neural network model to determine the circuit and network level mechanisms behind psilocybin's state-dependent effects on neural activity.
3. To develop a biophysically-inspired neural network model of the human cortex, to test whether the effects of psilocybin on neural circuit physiology, and the serotonin receptor expression in the human brain can account for psilocybin's ability to alter conscious perception.

This project will create an open software platform and a framework for analysis and interpretation of the effects of psychoactive drugs, informing both discovery neuroscience and drug development.