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Dendro-somatic Coupling and global neuronal signaling

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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Coordinator

HUMBOLDT-UNIVERSITAET ZU BERLIN
Net EU contribution
€ 2 303 750,00
Address
Unter Den Linden 6
10117 Berlin
Germany

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Region
Baden-Württemberg Stuttgart Stuttgart, Stadtkreis
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00

Participants (1)

IDRYMA TECHNOLOGIAS KAI EREVNAS
Greece
Net EU contribution
€ 196 250,00
Address
N Plastira Str 100
70013 Irakleio

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Region
Ηράκλειο Κρήτη Νησιά Αιγαίου
Activity type
Research Organisations
Non-EU contribution
€ 0,00