Project acronym BRAINSIGNALS
Project Optical dissection of circuits underlying fast cholinergic signalling during cognitive behaviour
Researcher (PI) Huibert Mansvelder
Host Institution (HI) STICHTING VU
Call Details Starting Grant (StG), LS5, ERC-2011-StG_20101109
Summary Our ability to think, to memorize and focus our thoughts depends on acetylcholine signaling in the brain. The loss of cholinergic signalling in for instance Alzheimer’s disease strongly compromises these cognitive abilities. The traditional view on the role of cholinergic input to the neocortex is that slowly changing levels of extracellular acetylcholine (ACh) mediate different arousal states. This view has been challenged by recent studies demonstrating that rapid phasic changes in ACh levels at the scale of seconds are correlated with focus of attention, suggesting that these signals may mediate defined cognitive operations. Despite a wealth of anatomical data on the organization of the cholinergic system, very little understanding exists on its functional organization. How the relatively sparse input of cholinergic transmission in the prefrontal cortex elicits such a profound and specific control over attention is unknown. The main objective of this proposal is to develop a causal understanding of how cellular mechanisms of fast acetylcholine signalling are orchestrated during cognitive behaviour.
In a series of studies, I have identified several synaptic and cellular mechanisms by which the cholinergic system can alter neuronal circuitry function, both in cortical and subcortical areas. I have used a combination of behavioral, physiological and genetic methods in which I manipulated cholinergic receptor functionality in prefrontal cortex in a subunit specific manner and found that ACh receptors in the prefrontal cortex control attention performance. Recent advances in optogenetic and electrochemical methods now allow to rapidly manipulate and measure acetylcholine levels in freely moving, behaving animals. Using these techniques, I aim to uncover which cholinergic neurons are involved in fast cholinergic signaling during cognition and uncover the underlying neuronal mechanisms that alter prefrontal cortical network function.
Summary
Our ability to think, to memorize and focus our thoughts depends on acetylcholine signaling in the brain. The loss of cholinergic signalling in for instance Alzheimer’s disease strongly compromises these cognitive abilities. The traditional view on the role of cholinergic input to the neocortex is that slowly changing levels of extracellular acetylcholine (ACh) mediate different arousal states. This view has been challenged by recent studies demonstrating that rapid phasic changes in ACh levels at the scale of seconds are correlated with focus of attention, suggesting that these signals may mediate defined cognitive operations. Despite a wealth of anatomical data on the organization of the cholinergic system, very little understanding exists on its functional organization. How the relatively sparse input of cholinergic transmission in the prefrontal cortex elicits such a profound and specific control over attention is unknown. The main objective of this proposal is to develop a causal understanding of how cellular mechanisms of fast acetylcholine signalling are orchestrated during cognitive behaviour.
In a series of studies, I have identified several synaptic and cellular mechanisms by which the cholinergic system can alter neuronal circuitry function, both in cortical and subcortical areas. I have used a combination of behavioral, physiological and genetic methods in which I manipulated cholinergic receptor functionality in prefrontal cortex in a subunit specific manner and found that ACh receptors in the prefrontal cortex control attention performance. Recent advances in optogenetic and electrochemical methods now allow to rapidly manipulate and measure acetylcholine levels in freely moving, behaving animals. Using these techniques, I aim to uncover which cholinergic neurons are involved in fast cholinergic signaling during cognition and uncover the underlying neuronal mechanisms that alter prefrontal cortical network function.
Max ERC Funding
1 499 242 €
Duration
Start date: 2011-11-01, End date: 2016-10-31
Project acronym CanISeeQG
Project Can I see Quantum Gravity?
Researcher (PI) Jan DE BOER
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Advanced Grant (AdG), PE2, ERC-2018-ADG
Summary The interplay between two of the most important building blocks of nature, quantum mechanics and gravity, has been a great source of inspiration for theoretical physics, leading to discoveries such as the Hawking radiation of black holes and the development of string theory. In turn, the following picture emerged: physics at the most fundamental level is governed by the rules of quantum mechanics while gravity is some effective coarse-grained description of the underlying microscopic theory. Given that the microscopic degrees of freedom are non-local, standard techniques such as the renormalization group and effective field theory a priori do not apply. Nevertheless, we use effective field theories that incorporate general relativity to describe our observations.
With the discovery of gravitational waves and the various ongoing and upcoming experiments that will put general relativity to the test, it has become urgent to assess the validity of the standard framework of effective field theory for describing observable quantum gravity effects. Recent developments in resolving the information loss paradox and the quantum nature of black holes concluded that effective field theory must be modified in a way that uniquely incorporates quantum gravity. The main purpose of this proposal is to describe this modification in a precise and quantitative way, ultimately connecting it to potential experimental discoveries.
In order to achieve this goal, I will approach the problem using a combination of thermodynamics, hydrodynamics and quantum information theory, mostly in the context of the AdS/CFT correspondence, where a precise description of quantum gravity is available. As a by-product of identifying observational features of quantum gravity, I will also make substantial progress in several foundational problems. My broad track record and expertise, and the fact that I have already obtained promising preliminary results, makes me uniquely qualified to lead this endeavor.
Summary
The interplay between two of the most important building blocks of nature, quantum mechanics and gravity, has been a great source of inspiration for theoretical physics, leading to discoveries such as the Hawking radiation of black holes and the development of string theory. In turn, the following picture emerged: physics at the most fundamental level is governed by the rules of quantum mechanics while gravity is some effective coarse-grained description of the underlying microscopic theory. Given that the microscopic degrees of freedom are non-local, standard techniques such as the renormalization group and effective field theory a priori do not apply. Nevertheless, we use effective field theories that incorporate general relativity to describe our observations.
With the discovery of gravitational waves and the various ongoing and upcoming experiments that will put general relativity to the test, it has become urgent to assess the validity of the standard framework of effective field theory for describing observable quantum gravity effects. Recent developments in resolving the information loss paradox and the quantum nature of black holes concluded that effective field theory must be modified in a way that uniquely incorporates quantum gravity. The main purpose of this proposal is to describe this modification in a precise and quantitative way, ultimately connecting it to potential experimental discoveries.
In order to achieve this goal, I will approach the problem using a combination of thermodynamics, hydrodynamics and quantum information theory, mostly in the context of the AdS/CFT correspondence, where a precise description of quantum gravity is available. As a by-product of identifying observational features of quantum gravity, I will also make substantial progress in several foundational problems. My broad track record and expertise, and the fact that I have already obtained promising preliminary results, makes me uniquely qualified to lead this endeavor.
Max ERC Funding
2 500 000 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym CCC
Project Cracking the Cerebellar Code
Researcher (PI) Christiaan Innocentius De Zeeuw
Host Institution (HI) ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Call Details Advanced Grant (AdG), LS5, ERC-2011-ADG_20110310
Summary Spike trains transfer information to and from neurons. Most studies so far assume that the average firing rate or “rate coding” is the predominant way of information coding. However, spikes occur at millisecond precision, and their actual timing or “temporal coding” can in principle strongly increase the information content of spike trains. The two coding mechanisms are not mutually exclusive. Neurons may switch between rate and temporal coding, or use a combination of both coding mechanisms at the same time, which would increase the information content of spike trains even further. Here, we propose to investigate the hypothesis that temporal coding plays, next to rate coding, important and specific roles in cerebellar processing during learning. The cerebellum is ideal to study this timely topic, because it has a clear anatomy with well-organized modules and matrices, a well-described physiology of different types of neurons with distinguishable spiking activity, and a central role in various forms of tractable motor learning. Moreover, uniquely in the brain, the main types of neurons in the cerebellar system can be genetically manipulated in a cell-specific fashion, which will allow us to investigate the behavioural importance of both coding mechanisms following cell-specific interference and/or during cell-specific visual imaging. Thus, for this proposal we will create conditional mouse mutants that will be subjected to learning paradigms in which we can disentangle the contributions of rate coding and temporal coding using electrophysiological and optogenetic recordings and stimulation. Together, our experiments should elucidate how neurons in the brain communicate during natural learning behaviour and how one may be able to intervene in this process to affect or improve procedural learning skills.
Summary
Spike trains transfer information to and from neurons. Most studies so far assume that the average firing rate or “rate coding” is the predominant way of information coding. However, spikes occur at millisecond precision, and their actual timing or “temporal coding” can in principle strongly increase the information content of spike trains. The two coding mechanisms are not mutually exclusive. Neurons may switch between rate and temporal coding, or use a combination of both coding mechanisms at the same time, which would increase the information content of spike trains even further. Here, we propose to investigate the hypothesis that temporal coding plays, next to rate coding, important and specific roles in cerebellar processing during learning. The cerebellum is ideal to study this timely topic, because it has a clear anatomy with well-organized modules and matrices, a well-described physiology of different types of neurons with distinguishable spiking activity, and a central role in various forms of tractable motor learning. Moreover, uniquely in the brain, the main types of neurons in the cerebellar system can be genetically manipulated in a cell-specific fashion, which will allow us to investigate the behavioural importance of both coding mechanisms following cell-specific interference and/or during cell-specific visual imaging. Thus, for this proposal we will create conditional mouse mutants that will be subjected to learning paradigms in which we can disentangle the contributions of rate coding and temporal coding using electrophysiological and optogenetic recordings and stimulation. Together, our experiments should elucidate how neurons in the brain communicate during natural learning behaviour and how one may be able to intervene in this process to affect or improve procedural learning skills.
Max ERC Funding
2 499 600 €
Duration
Start date: 2012-04-01, End date: 2017-03-31
Project acronym CMTaaRS
Project Defective protein translation as a pathogenic mechanism of peripheral neuropathy
Researcher (PI) Erik Jan Marthe STORKEBAUM
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Consolidator Grant (CoG), LS5, ERC-2017-COG
Summary Familial forms of neurodegenerative diseases are caused by mutations in a single gene. It is unknown whether distinct mutations in the same gene or in functionally related genes cause disease through similar or disparate mechanisms. Furthermore, the precise molecular mechanisms underlying virtually all neurodegenerative disorders are poorly understood, and effective treatments are typically lacking.
This is also the case for Charcot-Marie-Tooth (CMT) peripheral neuropathy caused by mutations in five distinct tRNA synthetase (aaRS) genes. We previously generated Drosophila CMT-aaRS models and used a novel method for cell-type-specific labeling of newly synthesized proteins in vivo to show that impaired protein translation may represent a common pathogenic mechanism.
In this proposal, I aim to determine whether translation is also inhibited in CMT-aaRS mouse models, and whether all mutations cause disease through gain-of-toxic-function, or alternatively, whether some mutations act through a dominant-negative mechanism. In addition, I will evaluate whether all CMT-aaRS mutant proteins inhibit translation, and I will test the hypothesis, raised by our unpublished preliminary data shown here, that a defect in the transfer of the (aminoacylated) tRNA from the mutant synthetase to elongation factor eEF1A is the molecular mechanism underlying CMT-aaRS. Finally, I will validate the identified molecular mechanism in CMT-aaRS mouse models, as the most disease-relevant mammalian model.
I expect to elucidate whether all CMT-aaRS mutations cause disease through a common molecular mechanism that involves inhibition of translation. This is of key importance from a therapeutic perspective, as a common pathogenic mechanism allows for a unified therapeutic approach. Furthermore, this proposal has the potential to unravel the detailed molecular mechanism underlying CMT-aaRS, what would constitute a breakthrough and a requirement for rational drug design for this incurable disease.
Summary
Familial forms of neurodegenerative diseases are caused by mutations in a single gene. It is unknown whether distinct mutations in the same gene or in functionally related genes cause disease through similar or disparate mechanisms. Furthermore, the precise molecular mechanisms underlying virtually all neurodegenerative disorders are poorly understood, and effective treatments are typically lacking.
This is also the case for Charcot-Marie-Tooth (CMT) peripheral neuropathy caused by mutations in five distinct tRNA synthetase (aaRS) genes. We previously generated Drosophila CMT-aaRS models and used a novel method for cell-type-specific labeling of newly synthesized proteins in vivo to show that impaired protein translation may represent a common pathogenic mechanism.
In this proposal, I aim to determine whether translation is also inhibited in CMT-aaRS mouse models, and whether all mutations cause disease through gain-of-toxic-function, or alternatively, whether some mutations act through a dominant-negative mechanism. In addition, I will evaluate whether all CMT-aaRS mutant proteins inhibit translation, and I will test the hypothesis, raised by our unpublished preliminary data shown here, that a defect in the transfer of the (aminoacylated) tRNA from the mutant synthetase to elongation factor eEF1A is the molecular mechanism underlying CMT-aaRS. Finally, I will validate the identified molecular mechanism in CMT-aaRS mouse models, as the most disease-relevant mammalian model.
I expect to elucidate whether all CMT-aaRS mutations cause disease through a common molecular mechanism that involves inhibition of translation. This is of key importance from a therapeutic perspective, as a common pathogenic mechanism allows for a unified therapeutic approach. Furthermore, this proposal has the potential to unravel the detailed molecular mechanism underlying CMT-aaRS, what would constitute a breakthrough and a requirement for rational drug design for this incurable disease.
Max ERC Funding
2 000 000 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym CoordinatedDopamine
Project Coordination of regional dopamine release in the striatum during habit formation and compulsive behaviour
Researcher (PI) Ingo Willuhn
Host Institution (HI) ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary The basal ganglia consist of a set of neuroanatomical structures that participate in the representation and execution of action sequences. Dopamine neurotransmission in the striatum, the main input nucleus of the basal ganglia, is a fundamental mechanism involved in learning and regulation of such actions. The striatum has multiple functional units, where the limbic striatum is thought to mediate motivational aspects of actions (e.g., goal-directedness) and the sensorimotor striatum their automation (e.g., habit formation). A long-standing question in the field is how limbic and sensorimotor domains communicate with each other, and specifically if they do so during the automation of action sequences. It has been suggested that such coordination is implemented by reciprocal loop connections between striatal projection neurons and the dopaminergic midbrain. Although very influential in theory the effectiveness of this limbic-sensorimotor “bridging” principle has yet to be verified. I hypothesize that during the automation of behaviour regional dopamine signalling is governed by a striatal hierarchy and that dysregulation of this coordination leads to compulsive execution of automatic actions characteristic of several psychiatric disorders. To test this hypothesis, we will conduct electrochemical measurements with real-time resolution simultaneously in limbic and sensorimotor striatum to assess the regional coordination of dopamine release in behaving animals. We developed novel chronically implantable electrodes to enable monitoring of dopamine dynamics throughout the development of habitual behaviour and its compulsive execution in transgenic rats - a species suitable for our complex behavioural assays. Novel rabies virus-mediated gene delivery for in vivo optogenetics in these rats will give us the unique opportunity to test whether specific loop pathways govern striatal dopamine transmission and are causally involved in habit formation and compulsive behaviour.
Summary
The basal ganglia consist of a set of neuroanatomical structures that participate in the representation and execution of action sequences. Dopamine neurotransmission in the striatum, the main input nucleus of the basal ganglia, is a fundamental mechanism involved in learning and regulation of such actions. The striatum has multiple functional units, where the limbic striatum is thought to mediate motivational aspects of actions (e.g., goal-directedness) and the sensorimotor striatum their automation (e.g., habit formation). A long-standing question in the field is how limbic and sensorimotor domains communicate with each other, and specifically if they do so during the automation of action sequences. It has been suggested that such coordination is implemented by reciprocal loop connections between striatal projection neurons and the dopaminergic midbrain. Although very influential in theory the effectiveness of this limbic-sensorimotor “bridging” principle has yet to be verified. I hypothesize that during the automation of behaviour regional dopamine signalling is governed by a striatal hierarchy and that dysregulation of this coordination leads to compulsive execution of automatic actions characteristic of several psychiatric disorders. To test this hypothesis, we will conduct electrochemical measurements with real-time resolution simultaneously in limbic and sensorimotor striatum to assess the regional coordination of dopamine release in behaving animals. We developed novel chronically implantable electrodes to enable monitoring of dopamine dynamics throughout the development of habitual behaviour and its compulsive execution in transgenic rats - a species suitable for our complex behavioural assays. Novel rabies virus-mediated gene delivery for in vivo optogenetics in these rats will give us the unique opportunity to test whether specific loop pathways govern striatal dopamine transmission and are causally involved in habit formation and compulsive behaviour.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym COSI
Project Cerebellar modules and the Ontogeny of Sensorimotor Integration
Researcher (PI) Martijn Schonewille
Host Institution (HI) ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Call Details Starting Grant (StG), LS5, ERC-2015-STG
Summary The perfect execution of a voluntary movement requires the appropriate integration of current bodily state, sensory input and desired outcome. To assure that this motor output becomes and remains appropriate, the brain needs to learn from the result of previous outputs. The cerebellum plays a central role in sensorimotor integration, yet -despite decades of studies- there is no generally excepted theory for cerebellar functioning. I recently demonstrated that cerebellar modules, identified based on anatomical connectivity and gene expression, differ distinctly in spike activity properties. It is my long-term goal to identify the ontogeny of anatomical and physiological differences between modules, and their functional consequences. My hypothesis is that these differences can explain existing controversies, and unify contradicting results into one central theory.
To this end, I have designed three key objectives. First, I will identify the development of connectivity and activity patterns at the input stage of the cerebellar cortex in relation to the cerebellar modules (key objective A). Next, I will relate the differences in gene expression levels between modules to differences in basal activity and strength of plasticity mechanisms in juvenile mice (key objective B). Finally, I will determine how module specific output develops in relation to behavior and what the effect of module specific mutations is on cerebellum-dependent motor tasks and higher order functions (key objective C).
Ultimately, the combined results of all key objectives will reveal how distinct difference between cerebellar modules develop, and how this ensemble ensures proper cerebellar information processing for optimal coordination of timing and force of movements. Combined with the growing body of evidence for a cerebellar role in higher order brain functions and neurodevelopmental disorders, a unifying theory would be fundamental for understanding how the juvenile brain develops.
Summary
The perfect execution of a voluntary movement requires the appropriate integration of current bodily state, sensory input and desired outcome. To assure that this motor output becomes and remains appropriate, the brain needs to learn from the result of previous outputs. The cerebellum plays a central role in sensorimotor integration, yet -despite decades of studies- there is no generally excepted theory for cerebellar functioning. I recently demonstrated that cerebellar modules, identified based on anatomical connectivity and gene expression, differ distinctly in spike activity properties. It is my long-term goal to identify the ontogeny of anatomical and physiological differences between modules, and their functional consequences. My hypothesis is that these differences can explain existing controversies, and unify contradicting results into one central theory.
To this end, I have designed three key objectives. First, I will identify the development of connectivity and activity patterns at the input stage of the cerebellar cortex in relation to the cerebellar modules (key objective A). Next, I will relate the differences in gene expression levels between modules to differences in basal activity and strength of plasticity mechanisms in juvenile mice (key objective B). Finally, I will determine how module specific output develops in relation to behavior and what the effect of module specific mutations is on cerebellum-dependent motor tasks and higher order functions (key objective C).
Ultimately, the combined results of all key objectives will reveal how distinct difference between cerebellar modules develop, and how this ensemble ensures proper cerebellar information processing for optimal coordination of timing and force of movements. Combined with the growing body of evidence for a cerebellar role in higher order brain functions and neurodevelopmental disorders, a unifying theory would be fundamental for understanding how the juvenile brain develops.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym DCVFUSION
Project Telling the full story: how neurons send other signals than by classical synaptic transmission
Researcher (PI) Matthijs Verhage
Host Institution (HI) STICHTING VUMC
Call Details Advanced Grant (AdG), LS5, ERC-2012-ADG_20120314
Summary The regulated secretion of chemical signals in the brain occurs principally from two organelles, synaptic vesicles and dense core vesicles (DCVs). Synaptic vesicle secretion accounts for the well characterized local, fast signalling in synapses. DCVs contain a diverse collection of cargo, including many neuropeptides that trigger a multitude of modulatory effects with quite robust impact, for instance on memory, mood, pain, appetite or social behavior. Disregulation of neuropeptide secretion is firmly associated with many diseases such as cognitive and mood disorders, obesity and diabetes. In addition, many other signals depend on DCVs, for instance trophic factors and proteolytic enzymes, but also signals that typically do not diffuse like guidance cues and pre-assembled active zones. Hence, it is beyond doubt that DCV signalling is a central factor in brain communication. However, many fundamental questions remain open on DCV trafficking and secretion. Therefore, the aim of this proposal is to characterize the molecular principles that account for DCV delivery at release sites and their secretion. I will address 4 fundamental questions: What are the molecular factors that drive DCV fusion in mammalian CNS neurons? How does Ca2+ trigger DCV fusion? What are the requirements of DCV release sites and where do they occur? Can DCV fusion be targeted to synthetic release sites in vivo? I will exploit >30 mutant mouse lines and new cell biological and photonic approaches that allow for the first time a quantitative assessment of DCV-trafficking and fusion of many cargo types, in living neurons with a single vesicle resolution. Preliminary data suggest that DCV secretion is quite different from synaptic vesicle and chromaffin granule secretion. Together, these studies will produce the first systematic evaluation of the molecular identity of the core machinery that drives DCV fusion in neurons, the Ca2+-affinity of DCV fusion and the characteristics of DCV release sites.
Summary
The regulated secretion of chemical signals in the brain occurs principally from two organelles, synaptic vesicles and dense core vesicles (DCVs). Synaptic vesicle secretion accounts for the well characterized local, fast signalling in synapses. DCVs contain a diverse collection of cargo, including many neuropeptides that trigger a multitude of modulatory effects with quite robust impact, for instance on memory, mood, pain, appetite or social behavior. Disregulation of neuropeptide secretion is firmly associated with many diseases such as cognitive and mood disorders, obesity and diabetes. In addition, many other signals depend on DCVs, for instance trophic factors and proteolytic enzymes, but also signals that typically do not diffuse like guidance cues and pre-assembled active zones. Hence, it is beyond doubt that DCV signalling is a central factor in brain communication. However, many fundamental questions remain open on DCV trafficking and secretion. Therefore, the aim of this proposal is to characterize the molecular principles that account for DCV delivery at release sites and their secretion. I will address 4 fundamental questions: What are the molecular factors that drive DCV fusion in mammalian CNS neurons? How does Ca2+ trigger DCV fusion? What are the requirements of DCV release sites and where do they occur? Can DCV fusion be targeted to synthetic release sites in vivo? I will exploit >30 mutant mouse lines and new cell biological and photonic approaches that allow for the first time a quantitative assessment of DCV-trafficking and fusion of many cargo types, in living neurons with a single vesicle resolution. Preliminary data suggest that DCV secretion is quite different from synaptic vesicle and chromaffin granule secretion. Together, these studies will produce the first systematic evaluation of the molecular identity of the core machinery that drives DCV fusion in neurons, the Ca2+-affinity of DCV fusion and the characteristics of DCV release sites.
Max ERC Funding
2 439 315 €
Duration
Start date: 2013-05-01, End date: 2019-04-30
Project acronym DYNAMINT
Project Dynamics of Probed, Pulsed, Quenched and Driven Integrable Quantum Systems
Researcher (PI) Jean-Sébastien CAUX
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Advanced Grant (AdG), PE2, ERC-2016-ADG
Summary This proposal intends to develop and apply a new-generation theoretical toolbox for understanding the rich dynamics of strongly-interacting many-body quantum sytems subjected to destabilizing manipulations bringing them very far from equilibrium.
In atomic systems, condensed matter and nanophysics settings, quantum matter is nowadays routinely pushed beyond the traditional low-energy/linear response/thermal equilibrium paradigms. Some experiments even clearly highlight the need to revise basic fundamental quantum statistical mechanics notions such as ergodicity, relaxation and thermalization in order to explain their behaviour. Theory must thus urgently revise its textbooks and develop new interpretations and capabilities for offering concrete, quantitative phenomenology.
This proposal is focused on a set of systems at the very center of this strongly-correlated, experimentally realizable far-from-equilibrium spectacle: integrable models of quantum spin chains, interacting gases confined to one spatial dimension, and quantum dots. Building up on recent theoretical breakthroughs in dynamical correlations and post-quench steady states, this proposal aims to shed a new light on the fundamental principles at the heart of many-body quantum dynamics. It will implement a broad and ambitious research agenda consisting of synergetic projects from mathematically formal thought experiments all the way to phenomenologically applied practical calculations. The types of protocols to be studied include probes creating high-energy excitations, pulses inducing changes beyond linear response, quenches causing sudden global reorganizations, all the way to drivings completely metamorphozing the physical states.
The result will be to provide reliable, experimentally relevant and urgently-needed theoretical `anchoring points' in our general understanding of the physics underlying far-from-equilibrium strongly-interacting quantum matter.
Summary
This proposal intends to develop and apply a new-generation theoretical toolbox for understanding the rich dynamics of strongly-interacting many-body quantum sytems subjected to destabilizing manipulations bringing them very far from equilibrium.
In atomic systems, condensed matter and nanophysics settings, quantum matter is nowadays routinely pushed beyond the traditional low-energy/linear response/thermal equilibrium paradigms. Some experiments even clearly highlight the need to revise basic fundamental quantum statistical mechanics notions such as ergodicity, relaxation and thermalization in order to explain their behaviour. Theory must thus urgently revise its textbooks and develop new interpretations and capabilities for offering concrete, quantitative phenomenology.
This proposal is focused on a set of systems at the very center of this strongly-correlated, experimentally realizable far-from-equilibrium spectacle: integrable models of quantum spin chains, interacting gases confined to one spatial dimension, and quantum dots. Building up on recent theoretical breakthroughs in dynamical correlations and post-quench steady states, this proposal aims to shed a new light on the fundamental principles at the heart of many-body quantum dynamics. It will implement a broad and ambitious research agenda consisting of synergetic projects from mathematically formal thought experiments all the way to phenomenologically applied practical calculations. The types of protocols to be studied include probes creating high-energy excitations, pulses inducing changes beyond linear response, quenches causing sudden global reorganizations, all the way to drivings completely metamorphozing the physical states.
The result will be to provide reliable, experimentally relevant and urgently-needed theoretical `anchoring points' in our general understanding of the physics underlying far-from-equilibrium strongly-interacting quantum matter.
Max ERC Funding
2 444 446 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym EMERGRAV
Project Emergent Gravity, String Theory and the Holographic Principle
Researcher (PI) Erik Peter Verlinde
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Advanced Grant (AdG), PE2, ERC-2010-AdG_20100224
Summary The study of black hole physics and string theory are leading to a novel perspective on gravity and space-time. The old frameworks are replaced by a new paradigm in which gravity is understood as an emergent phenomenon. A central role in this revolution is played by the holographic principle put forward by ‘t Hooft. It states that the microscopic information associated with the physical world can be stored on the boundary of space. From this holographic viewpoint I have recently derived the familiar laws of Newton and Einstein using only first principles. Gravity appears as an entropic force caused by changes in information associated with matter. With this ERC proposal I am aiming to build a research group that will further develop this new entropic view on gravity. The powerful string theoretic tools, such as the holographic correspondence between gauge theory and gravity, will be used to illuminate and further clarify gravity’s entropic origin. In addition, I plan to investigate the implications of the emergence of the gravitational force for the areas in which gravity plays a crucial role, in particular cosmology. For instance, the entropic viewpoint is expected to shed new light on the nature of dark energy and possibly dark matter. It may also lead to a new perspective on the other fundamental forces, since the notions of inertia and mass need to be reconsidered as well. The understanding of gravity as an emergent phenomenon will also influence and benefit from the conceptual ideas developed in condensed matter physics, such as the recently discovered connection between quantum critical electron systems and black hole horizons. The university of Amsterdam and the Netherlands provide an excellent environment for a successful completion of these goals.
Summary
The study of black hole physics and string theory are leading to a novel perspective on gravity and space-time. The old frameworks are replaced by a new paradigm in which gravity is understood as an emergent phenomenon. A central role in this revolution is played by the holographic principle put forward by ‘t Hooft. It states that the microscopic information associated with the physical world can be stored on the boundary of space. From this holographic viewpoint I have recently derived the familiar laws of Newton and Einstein using only first principles. Gravity appears as an entropic force caused by changes in information associated with matter. With this ERC proposal I am aiming to build a research group that will further develop this new entropic view on gravity. The powerful string theoretic tools, such as the holographic correspondence between gauge theory and gravity, will be used to illuminate and further clarify gravity’s entropic origin. In addition, I plan to investigate the implications of the emergence of the gravitational force for the areas in which gravity plays a crucial role, in particular cosmology. For instance, the entropic viewpoint is expected to shed new light on the nature of dark energy and possibly dark matter. It may also lead to a new perspective on the other fundamental forces, since the notions of inertia and mass need to be reconsidered as well. The understanding of gravity as an emergent phenomenon will also influence and benefit from the conceptual ideas developed in condensed matter physics, such as the recently discovered connection between quantum critical electron systems and black hole horizons. The university of Amsterdam and the Netherlands provide an excellent environment for a successful completion of these goals.
Max ERC Funding
2 033 983 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym ENCODING IN AXONS
Project Identifying mechanisms of information encoding in myelinated single axons
Researcher (PI) Maarten Kole
Host Institution (HI) KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary A major challenge in neuroscience is to understand how information is stored and coded within single nerve cells (neurons) and across neuron populations in the brain. Nerve cell fibres (axons) are thought to provide the wiring to connect neurons and conduct the electrical nerve impulse (action potential; AP). Recent discoveries, however, show that the initial part of axons actively participates in modulating APs and providing a means to enhance the computational repertoire of neurons in the central nervous system. To decrease the temporal delay in information transmission over long distances most axons are myelinated. Here, we will test the hypothesis that the degree of myelination of single axons directly and indirectly influences the mechanisms of AP generation and neural coding. We will use a novel approach of patch-clamp recording combined with immunohistochemical and ultrastructural identification to develop a detailed model of single myelinated neocortical axons. We also will investigate the neuron-glia interactions responsible for the myelination process and measure whether their development follows an activity-dependent process. Finally, we will elucidate the physiological and molecular similarities and discrepancies between myelinated and experimentally demyelinated single neocortical axons. These studies will provide a novel methodological framework to study central nervous system axons and yield basic insights into myelin physiology and pathophysiology.
Summary
A major challenge in neuroscience is to understand how information is stored and coded within single nerve cells (neurons) and across neuron populations in the brain. Nerve cell fibres (axons) are thought to provide the wiring to connect neurons and conduct the electrical nerve impulse (action potential; AP). Recent discoveries, however, show that the initial part of axons actively participates in modulating APs and providing a means to enhance the computational repertoire of neurons in the central nervous system. To decrease the temporal delay in information transmission over long distances most axons are myelinated. Here, we will test the hypothesis that the degree of myelination of single axons directly and indirectly influences the mechanisms of AP generation and neural coding. We will use a novel approach of patch-clamp recording combined with immunohistochemical and ultrastructural identification to develop a detailed model of single myelinated neocortical axons. We also will investigate the neuron-glia interactions responsible for the myelination process and measure whether their development follows an activity-dependent process. Finally, we will elucidate the physiological and molecular similarities and discrepancies between myelinated and experimentally demyelinated single neocortical axons. These studies will provide a novel methodological framework to study central nervous system axons and yield basic insights into myelin physiology and pathophysiology.
Max ERC Funding
1 994 640 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
