Periodic Reporting for period 1 - Cortical Coupling (Dendro-somatic Coupling and global neuronal signaling)
Berichtszeitraum: 2023-01-01 bis 2025-06-30
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.
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.
The contribution of FORTH in this projects starts on Year three, namely from January 1st 2025 until December 31st 2027. Thus, for the first reporting period there were no activities undertaken by the FORTH team.
The CorticalCoupling project is pioneering new frontiers in understanding how our brain cells compute and how consciousness arises. Our work is already yielding results that push beyond current scientific boundaries, with exciting potential impacts:
One of our most significant breakthroughs is a new way to study live human brain tissue with unprecedented speed and precision. We've developed an "ultra-fast" viral system that allows us to introduce tools for observing and controlling neurons into surgically resected human brain slices within just hours. Previously, such experiments were largely impossible due to the slow nature of available tools. This innovation is like giving neuroscientists a high-speed camera and remote control for human brain circuits, opening the door to directly understanding human-specific brain functions, the cellular basis of neurological disorders, and even testing new therapies on human tissue. To ensure this powerful tool reaches its full potential, we aim to share our methods widely and explore collaborations for broader distribution.
Building on this, we are making the first detailed exploration of "dendro-somatic coupling" (DSC) – the crucial connection between a neuron's 'antenna' and its main body – directly in human neurons. We're discovering how this coupling is dynamically controlled by chemical signals and how it changes under conditions like anaesthesia. This is a leap beyond rodent studies, as human neurons are much larger and their coupling mechanisms are vital for understanding how anaesthetics work and how consciousness is lost. Our findings could lead to safer anaesthesia, new ways to assess consciousness, and targets for treating cognitive disorders. Further research will be needed to link these cellular insights to whole-brain activity in humans.
In parallel, we've developed advanced techniques to track this dendritic communication in real-time within the brains of behaving animals. By combining high-density neural probes with precise light stimulation of dendrites, we can see exactly how these 'antennas' influence a neuron's decision to fire during different brain states like sleep and wakefulness. This bridges the gap between detailed cellular studies and understanding how the brain functions as a whole.
Finally, we're uncovering that even inhibitory "calming" neurons in the human brain have sophisticated processing capabilities in their own dendrites. This adds a new layer of complexity to how brain circuits are regulated, suggesting that these cells play a more dynamic role in shaping brain activity than previously thought.
In essence, CorticalCoupling is not just observing the brain; we are developing novel tools to actively probe and understand its most fundamental communication pathways, particularly in humans. Our early results are already changing how we can approach the study of the human brain and its most profound mysteries, like consciousness itself.
One of our most significant breakthroughs is a new way to study live human brain tissue with unprecedented speed and precision. We've developed an "ultra-fast" viral system that allows us to introduce tools for observing and controlling neurons into surgically resected human brain slices within just hours. Previously, such experiments were largely impossible due to the slow nature of available tools. This innovation is like giving neuroscientists a high-speed camera and remote control for human brain circuits, opening the door to directly understanding human-specific brain functions, the cellular basis of neurological disorders, and even testing new therapies on human tissue. To ensure this powerful tool reaches its full potential, we aim to share our methods widely and explore collaborations for broader distribution.
Building on this, we are making the first detailed exploration of "dendro-somatic coupling" (DSC) – the crucial connection between a neuron's 'antenna' and its main body – directly in human neurons. We're discovering how this coupling is dynamically controlled by chemical signals and how it changes under conditions like anaesthesia. This is a leap beyond rodent studies, as human neurons are much larger and their coupling mechanisms are vital for understanding how anaesthetics work and how consciousness is lost. Our findings could lead to safer anaesthesia, new ways to assess consciousness, and targets for treating cognitive disorders. Further research will be needed to link these cellular insights to whole-brain activity in humans.
In parallel, we've developed advanced techniques to track this dendritic communication in real-time within the brains of behaving animals. By combining high-density neural probes with precise light stimulation of dendrites, we can see exactly how these 'antennas' influence a neuron's decision to fire during different brain states like sleep and wakefulness. This bridges the gap between detailed cellular studies and understanding how the brain functions as a whole.
Finally, we're uncovering that even inhibitory "calming" neurons in the human brain have sophisticated processing capabilities in their own dendrites. This adds a new layer of complexity to how brain circuits are regulated, suggesting that these cells play a more dynamic role in shaping brain activity than previously thought.
In essence, CorticalCoupling is not just observing the brain; we are developing novel tools to actively probe and understand its most fundamental communication pathways, particularly in humans. Our early results are already changing how we can approach the study of the human brain and its most profound mysteries, like consciousness itself.