For over two centuries, anaesthesia has been a cornerstone of modern medicine, yet the precise mechanisms by which it induces unconsciousness have remained a significant puzzle for neuroscience. It's known that anaesthesia leads to a massive reduction in global brain signalling and a decoupling of crucial feedback information pathways. The CorticalCoupling project stems from a key discovery by our laboratory: during anaesthesia, the long 'antennas' (apical dendrites) of vital cortical brain cells (pyramidal neurons) are effectively disconnected from their cell bodies. We term this connection 'dendro-somatic coupling' and found it is maintained by specific chemical signals from deeper brain structures like the thalamus.
The central objective of CorticalCoupling is to comprehensively investigate this dendro-somatic coupling, which we hypothesise is a fundamental mechanism regulating the flow of information throughout the brain and the integration of feedback. We are exploring how this coupling works at the cellular level, how it's influenced by different brain states (like wakefulness, sleep, and anaesthesia), and its specific role in human brain cells, which are significantly larger and potentially more reliant on such coupling than those in rodents.
To achieve this, CorticalCoupling employs a multi-faceted approach. We use state-of-the-art techniques in rodent models, including advanced imaging, optogenetics (controlling neurons with light), and electrophysiology, both in vitro (brain slices) and in vivo (behaving animals). A groundbreaking aspect involves experiments on resected cortical tissue from human neurosurgical patients, using an ultra-fast viral gene delivery system developed within this project. This novel method allows us to introduce tools for observation and control into human neurons within hours, a significant advance for studying live human brain circuits. Finally, computational modelling is used to probe the consequences of dendro-somatic coupling for single-cell computation and the principles of complex neuronal networks.
The expected impact of CorticalCoupling is profound. A deeper understanding of dendro-somatic coupling promises to revolutionize our comprehension of fundamental cortical operations, how consciousness is maintained and lost, and the specific action of anaesthetics. This knowledge could pave the way for safer anaesthesia protocols and offer new insights into neurological and psychiatric conditions where consciousness or information processing is impaired. Furthermore, the principles uncovered could inspire the design of more efficient and brain-like artificial neural network architectures.
