Project description
Neuronal signalling under anaesthesia
Anaesthesia constitutes a great discovery, which has allowed man to perform surgical and other medical procedures without the patient feeling any pain. However, despite being used for years, it is not entirely clear how it works. The ERC-funded Cortical Coupling project aims to elucidate how it’s possible to lose consciousness under anaesthesia but retain neuronal signalling in the brain. The work focuses on pyramidal neurons and their dendritic structure and signal propagation at cellular level under consciousness and anaesthesia. Study results will provide important knowledge about anaesthesia and facilitate its improvement . At the same time, the work will bring scientists a step closer to comprehending the complexity of brain function.
Objective
"The mechanism for anaesthesia has eluded neuroscience despite being used as a medical intervention for more than two centuries. Two facts are clear: loss-of-consciousness under anaesthesia correlates with a massive reduction in global neuronal signalling and a de-coupling of feedback information. We recently found that the apical dendrites of layer 5 pyramidal neurons are effectively ""cut off"" from the cell body under anaesthesia and that higher order thalamic input maintains dendro-somatic coupling via the activation of metabotropic glutamate and acetylcholine receptors. We hypothesize that dendro-somatic coupling, the influence of the apical dendrite on the soma, regulates the flow of information around the brain. If true, this would mean that dendro-thalamic coupling is a ubiquitous mechanism by which the brain, via thalamo-cortical interactions, can regulate the degree to which feedback is reintegrated into any given cortical column. Moreover, since human pyramidal neurons are twice as long as rodent neurons, the issue of dendro-somatic coupling in human neurons is even more profound.
Here, we propose to comprehensively investigate this cortical coupling mechanism in vitro and in vivo using state-of-the-art approaches developed in my laboratory and specifically designed to investigate dendritic signalling. We will also perform experiments in resected cortical tissue from human patients using fast-viral expression of optogenetic constructs, an approach that we have also developed and tested in my laboratory. Lastly, we use modelling to probe the consequences of dendro-somatic coupling both for single-cell computation and the principles of multi-compartment neuronal networks.
Dendro-somatic coupling as a dynamic mechanism for global neuronal signalling is a bold new perspective for which we have clear evidence, and which stands to revolutionize our understanding of cortex and possibly also provide insights into more efficient neural network architectures.
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Fields of science
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
ERC - Support for frontier research (ERC)Host institution
10117 Berlin
Germany