Project acronym BrainBIT
Project All-optical brain-to-brain behaviour and information transfer
Researcher (PI) Francesco PAVONE
Host Institution (HI) UNIVERSITA DEGLI STUDI DI FIRENZE
Call Details Advanced Grant (AdG), PE2, ERC-2015-AdG
Summary Exchange of information between different brains usually takes place through the interaction between bodies and the external environment. The ultimate goal of this project is to establish a novel paradigm of brain-to-brain communication based on direct full-optical recording and controlled stimulation of neuronal activity in different subjects. To pursue this challenging objective, we propose to develop optical technologies well beyond the state of the art for simultaneous neuronal “reading” and “writing” across large volumes and with high spatial and temporal resolution, targeted to the transfer of advantageous behaviour in physiological and pathological conditions.
We will perform whole-brain high-resolution imaging in zebrafish larvae to disentangle the activity patterns related to different tasks. We will then use these patterns as stimulation templates in other larvae to investigate spatio-temporal subject-invariant signatures of specific behavioural states. This ‘pump and probe’ strategy will allow gaining deep insights into the complex relationship between neuronal activity and subject behaviour.
To move towards clinics-oriented studies on brain stimulation therapies, we will complement whole-brain experiments in zebrafish with large area functional imaging and optostimulation in mammals. We will investigate all-optical brain-to-brain information transfer to boost an advantageous behaviour, i.e. motor recovery, in a mouse model of stroke. Mice showing more effective responses to rehabilitation will provide neuronal activity templates to be elicited in other animals, in order to increase rehabilitation efficiency.
We strongly believe that the implementation of new technologies for all-optical transfer of behaviour between different subjects will offer unprecedented views of neuronal activity in healthy and injured brain, paving the way to more effective brain stimulation therapies.
Summary
Exchange of information between different brains usually takes place through the interaction between bodies and the external environment. The ultimate goal of this project is to establish a novel paradigm of brain-to-brain communication based on direct full-optical recording and controlled stimulation of neuronal activity in different subjects. To pursue this challenging objective, we propose to develop optical technologies well beyond the state of the art for simultaneous neuronal “reading” and “writing” across large volumes and with high spatial and temporal resolution, targeted to the transfer of advantageous behaviour in physiological and pathological conditions.
We will perform whole-brain high-resolution imaging in zebrafish larvae to disentangle the activity patterns related to different tasks. We will then use these patterns as stimulation templates in other larvae to investigate spatio-temporal subject-invariant signatures of specific behavioural states. This ‘pump and probe’ strategy will allow gaining deep insights into the complex relationship between neuronal activity and subject behaviour.
To move towards clinics-oriented studies on brain stimulation therapies, we will complement whole-brain experiments in zebrafish with large area functional imaging and optostimulation in mammals. We will investigate all-optical brain-to-brain information transfer to boost an advantageous behaviour, i.e. motor recovery, in a mouse model of stroke. Mice showing more effective responses to rehabilitation will provide neuronal activity templates to be elicited in other animals, in order to increase rehabilitation efficiency.
We strongly believe that the implementation of new technologies for all-optical transfer of behaviour between different subjects will offer unprecedented views of neuronal activity in healthy and injured brain, paving the way to more effective brain stimulation therapies.
Max ERC Funding
2 370 250 €
Duration
Start date: 2016-12-01, End date: 2021-11-30
Project acronym ENUBET
Project Enhanced NeUtrino BEams from kaon Tagging
Researcher (PI) Andrea Longhin
Host Institution (HI) ISTITUTO NAZIONALE DI FISICA NUCLEARE
Call Details Consolidator Grant (CoG), PE2, ERC-2015-CoG
Summary ENUBET has been designed to open a new window of opportunities in accelerator neutrino physics.
The proposed project enables for the first time the measurement of the positrons produced in the decay tunnel of conventional neutrino beams: these particles signal uniquely the generation of an electron neutrino at source.
Neutrino facilities enhanced by the ENUBET technique will have an unprecedented control of the neutrino flux. This will allow to reduce by one order of magnitude the uncertainties on neutrino cross sections: a leap that has been sought after since decades and that is needed to address the challenges of discovering matter-antimatter asymmetries in the leptonic sector.
The apparatus is a highly specialized electromagnetic calorimeter with fast response, sustaining particle rates as high as 0.5 MHz/cm^2, having excellent electron/pion separation capabilities with a reduced number of read-out channels. ENUBET will boost technologies that have been envisaged for high energy colliders to address this new challenge. On the other hand it will operate in a substantially different configuration. The experiment will be performed at the CERN Neutrino Platform, a recently approved facility where innovative neutrino detectors will be developed exploiting dedicated hadron beam-lines from the SPS accelerator. In the first phase of the project, ENUBET will address the challenges of particle identification from extended sources, developing innovative optical readout systems and cost-effective solutions for radiation imaging. This approach is based on cutting-edge technologies for single photon sensitive devices. During the second phase, the detector will be assembled and characterized at CERN with particle beams. Finally, it will be operated in time coincidence with Liquid Argon neutrino detectors, achieving a major step towards the realization of the concept of tagging individual neutrinos both at production and interaction level, on an event-by-event basis.
Summary
ENUBET has been designed to open a new window of opportunities in accelerator neutrino physics.
The proposed project enables for the first time the measurement of the positrons produced in the decay tunnel of conventional neutrino beams: these particles signal uniquely the generation of an electron neutrino at source.
Neutrino facilities enhanced by the ENUBET technique will have an unprecedented control of the neutrino flux. This will allow to reduce by one order of magnitude the uncertainties on neutrino cross sections: a leap that has been sought after since decades and that is needed to address the challenges of discovering matter-antimatter asymmetries in the leptonic sector.
The apparatus is a highly specialized electromagnetic calorimeter with fast response, sustaining particle rates as high as 0.5 MHz/cm^2, having excellent electron/pion separation capabilities with a reduced number of read-out channels. ENUBET will boost technologies that have been envisaged for high energy colliders to address this new challenge. On the other hand it will operate in a substantially different configuration. The experiment will be performed at the CERN Neutrino Platform, a recently approved facility where innovative neutrino detectors will be developed exploiting dedicated hadron beam-lines from the SPS accelerator. In the first phase of the project, ENUBET will address the challenges of particle identification from extended sources, developing innovative optical readout systems and cost-effective solutions for radiation imaging. This approach is based on cutting-edge technologies for single photon sensitive devices. During the second phase, the detector will be assembled and characterized at CERN with particle beams. Finally, it will be operated in time coincidence with Liquid Argon neutrino detectors, achieving a major step towards the realization of the concept of tagging individual neutrinos both at production and interaction level, on an event-by-event basis.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym GIANTSYN
Project Biophysics and circuit function of a giant cortical glutamatergic synapse
Researcher (PI) Peter Jonas
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Advanced Grant (AdG), LS5, ERC-2015-AdG
Summary A fundamental question in neuroscience is how the biophysical properties of synapses shape higher network
computations. The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells
and dendrites of CA3 pyramidal neurons, is the ideal synapse to address this question. This synapse is accessible
to presynaptic recording, due to its large size, allowing a rigorous investigation of the biophysical
mechanisms of transmission and plasticity. Furthermore, this synapse is placed in the center of a memory
circuit, and several hypotheses about its network function have been generated. However, even basic properties
of this key communication element remain enigmatic. The ambitious goal of the current proposal, GIANTSYN,
is to understand the hippocampal mossy fiber synapse at all levels of complexity. At the subcellular
level, we want to elucidate the biophysical mechanisms of transmission and synaptic plasticity in the
same depth as previously achieved at peripheral and brainstem synapses, classical synaptic models. At the
network level, we want to unravel the connectivity rules and the in vivo network function of this synapse,
particularly its role in learning and memory. To reach these objectives, we will combine functional and
structural approaches. For the analysis of synaptic transmission and plasticity, we will combine direct preand
postsynaptic patch-clamp recording and high-pressure freezing electron microscopy. For the analysis of
connectivity and network function, we will use transsynaptic labeling and in vivo electrophysiology. Based
on the proposed interdisciplinary research, the hippocampal mossy fiber synapse could become the first synapse
in the history of neuroscience in which we reach complete insight into both synaptic biophysics and
network function. In the long run, the results may open new perspectives for the diagnosis and treatment of
brain diseases in which mossy fiber transmission, plasticity, or connectivity are impaired.
Summary
A fundamental question in neuroscience is how the biophysical properties of synapses shape higher network
computations. The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells
and dendrites of CA3 pyramidal neurons, is the ideal synapse to address this question. This synapse is accessible
to presynaptic recording, due to its large size, allowing a rigorous investigation of the biophysical
mechanisms of transmission and plasticity. Furthermore, this synapse is placed in the center of a memory
circuit, and several hypotheses about its network function have been generated. However, even basic properties
of this key communication element remain enigmatic. The ambitious goal of the current proposal, GIANTSYN,
is to understand the hippocampal mossy fiber synapse at all levels of complexity. At the subcellular
level, we want to elucidate the biophysical mechanisms of transmission and synaptic plasticity in the
same depth as previously achieved at peripheral and brainstem synapses, classical synaptic models. At the
network level, we want to unravel the connectivity rules and the in vivo network function of this synapse,
particularly its role in learning and memory. To reach these objectives, we will combine functional and
structural approaches. For the analysis of synaptic transmission and plasticity, we will combine direct preand
postsynaptic patch-clamp recording and high-pressure freezing electron microscopy. For the analysis of
connectivity and network function, we will use transsynaptic labeling and in vivo electrophysiology. Based
on the proposed interdisciplinary research, the hippocampal mossy fiber synapse could become the first synapse
in the history of neuroscience in which we reach complete insight into both synaptic biophysics and
network function. In the long run, the results may open new perspectives for the diagnosis and treatment of
brain diseases in which mossy fiber transmission, plasticity, or connectivity are impaired.
Max ERC Funding
2 677 500 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym LoTGlasSy
Project Low Temperature Glassy Systems
Researcher (PI) Giorgio Parisi
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Call Details Advanced Grant (AdG), PE2, ERC-2015-AdG
Summary Jamming of hard spheres is a new critical phenomenon whose exponents are different from those of the other known transitions. These exponents have been recently computed in a mean field approximation whose limits of validity are not known. Even if their values are in very good agreement with the ones obtained by accurate numerical simulations, the deep reasons for this success are not understood.
Trampolining from these results I plan to develop a theory of the large scale properties of the free energy landscape of glasses at low temperature. I will use techniques of statistical field theory and of renormalization group to identify and compute universal features. This proposal has the following goals.
• We will develop a complete analytic theory of the infinite pressure limit (jamming) of hard spheres in dimensions greater than the upper critical dimensions. We will first compute analytically the upper critical dimension. Numerical simulations suggest that the upper critical dimensions is equal to or smaller than 2: this result is puzzling and it would be very interesting to find out if this indication is supported by the theory. We will also investigate in detail the scaling properties and the conformal invariance of the correlation functions.
• Starting from these results we will derive universal properties of glassy materials in the low temperature regions in the classical and in the quantum regime. The properties of multiple equilibrium configurations are crucial; we will study the structure of small (localized or extended) oscillations around them, the classical and quantum tunneling barriers.
• We will analyze both equilibrium features and off-equilibrium features (like plasticity and the time dependence of the specific heat). The subject has been widely discussed and phenomenological laws have been derived. I aim to obtain these laws from first principles using the properties of the free energy landscape in glasses that will be derived analytically.
Summary
Jamming of hard spheres is a new critical phenomenon whose exponents are different from those of the other known transitions. These exponents have been recently computed in a mean field approximation whose limits of validity are not known. Even if their values are in very good agreement with the ones obtained by accurate numerical simulations, the deep reasons for this success are not understood.
Trampolining from these results I plan to develop a theory of the large scale properties of the free energy landscape of glasses at low temperature. I will use techniques of statistical field theory and of renormalization group to identify and compute universal features. This proposal has the following goals.
• We will develop a complete analytic theory of the infinite pressure limit (jamming) of hard spheres in dimensions greater than the upper critical dimensions. We will first compute analytically the upper critical dimension. Numerical simulations suggest that the upper critical dimensions is equal to or smaller than 2: this result is puzzling and it would be very interesting to find out if this indication is supported by the theory. We will also investigate in detail the scaling properties and the conformal invariance of the correlation functions.
• Starting from these results we will derive universal properties of glassy materials in the low temperature regions in the classical and in the quantum regime. The properties of multiple equilibrium configurations are crucial; we will study the structure of small (localized or extended) oscillations around them, the classical and quantum tunneling barriers.
• We will analyze both equilibrium features and off-equilibrium features (like plasticity and the time dependence of the specific heat). The subject has been widely discussed and phenomenological laws have been derived. I aim to obtain these laws from first principles using the properties of the free energy landscape in glasses that will be derived analytically.
Max ERC Funding
1 760 000 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym MiniBrain
Project Cerebral Organoids: Using stem cell derived 3D cultures to understand human brain development and neurological disorders
Researcher (PI) Juergen Knoblich
Host Institution (HI) INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH
Call Details Advanced Grant (AdG), LS5, ERC-2015-AdG
Summary Most of our knowledge on human development and physiology is derived from experiments done in animal models. While these experiments have led to a comprehensive understanding of the principles of neurogenesis, animal models often fall short of modelling many of the most common neurological disorders. Recent experiments have revealed characteristic striking differences in brain development between rodents and primates and may provide an explanation for this problem.
The goal of this proposal is to use three dimensional organoid cultures derived from pluripotent human stem cells to reveal the human specific aspects of brain development and to analyse neurological disease mechanisms directly in human tissue. We have recently developed a 3D culture method allowing us to recapitulate human brain development during the first trimester of embryogenesis. Using this method, we will define the human specific brain patterning events in order to develop a culture system that can recapitulate essentially any part of the brain. Using a unique combination of cell type specific markers and mutagenic viruses, we will define the transcriptional networks defining specific neuronal subtypes. This will allow us to perform loss-of function genetics in human tissue to define transcription factors necessary for development of individual neuronal subtypes on a genome-wide level. Finally, we will apply the genome wide screening technology to human neurological disorders like microcephaly or schizophrenia to identify factors that can rescue disease phenotypes.
This research proposal will provide fundamental insights into the cellular and molecular mechanisms specifying various neuronal subclasses in the human brain and establish technology that can be applied to a variety of cell types and brain regions. The proposed experiments have the potential to yield fundamental insights into human neurological disease mechanisms that can currently not be derived from animal models.
Summary
Most of our knowledge on human development and physiology is derived from experiments done in animal models. While these experiments have led to a comprehensive understanding of the principles of neurogenesis, animal models often fall short of modelling many of the most common neurological disorders. Recent experiments have revealed characteristic striking differences in brain development between rodents and primates and may provide an explanation for this problem.
The goal of this proposal is to use three dimensional organoid cultures derived from pluripotent human stem cells to reveal the human specific aspects of brain development and to analyse neurological disease mechanisms directly in human tissue. We have recently developed a 3D culture method allowing us to recapitulate human brain development during the first trimester of embryogenesis. Using this method, we will define the human specific brain patterning events in order to develop a culture system that can recapitulate essentially any part of the brain. Using a unique combination of cell type specific markers and mutagenic viruses, we will define the transcriptional networks defining specific neuronal subtypes. This will allow us to perform loss-of function genetics in human tissue to define transcription factors necessary for development of individual neuronal subtypes on a genome-wide level. Finally, we will apply the genome wide screening technology to human neurological disorders like microcephaly or schizophrenia to identify factors that can rescue disease phenotypes.
This research proposal will provide fundamental insights into the cellular and molecular mechanisms specifying various neuronal subclasses in the human brain and establish technology that can be applied to a variety of cell types and brain regions. The proposed experiments have the potential to yield fundamental insights into human neurological disease mechanisms that can currently not be derived from animal models.
Max ERC Funding
2 800 000 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym PHOSPhOR
Project Photonics of Spin–Orbit Optical Phenomena
Researcher (PI) Lorenzo MARRUCCI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II
Call Details Advanced Grant (AdG), PE2, ERC-2015-AdG
Summary Spin-orbit optical phenomena can be broadly defined as those phenomena in which the polarization (“spin”) and the spatial structure (“orbit”) of an optical wave interact with each other and become spatially and/or temporally correlated, leading to novel effects or photonic applications.
The project vision is a full-fledged spin-orbit photonic science and technology, and its achievement will be pursued by moving in three main directions:
1) We will develop innovative systems based on spin-orbit optical media for generating light fields exhibiting a complex spatial vector structure, both in two dimensions (transverse plane and transverse fields) and in three (i.e. involving time- and space-dependent polarization fields and longitudinal field components). We will extend these ideas to other spectral domains (terahertz waves) and explore the possible applications of these fields in areas such as optical manipulation, plasmonics, space-division multiplexing in optical fibers, time-domain terahertz spectroscopy, ultrafast optics.
2) We will exploit spin-orbit quantum correlations generated within single photons and/or among few correlated photons to demonstrate novel quantum-information protocols using both the polarization and the transverse modes to encode and manipulate multiple qubits in each photon and for the implementation of quantum simulations of material systems based on photonic quantum walks in the Hilbert space of the light transverse modes.
3) We will investigate novel or unexplained physical processes occurring in structured optical media and light-sensitive material systems which respond both to the optical polarization and to its spatial inhomogeneity. Such materials will then be used to manipulate and characterize spin-orbit vector states of light.
Summary
Spin-orbit optical phenomena can be broadly defined as those phenomena in which the polarization (“spin”) and the spatial structure (“orbit”) of an optical wave interact with each other and become spatially and/or temporally correlated, leading to novel effects or photonic applications.
The project vision is a full-fledged spin-orbit photonic science and technology, and its achievement will be pursued by moving in three main directions:
1) We will develop innovative systems based on spin-orbit optical media for generating light fields exhibiting a complex spatial vector structure, both in two dimensions (transverse plane and transverse fields) and in three (i.e. involving time- and space-dependent polarization fields and longitudinal field components). We will extend these ideas to other spectral domains (terahertz waves) and explore the possible applications of these fields in areas such as optical manipulation, plasmonics, space-division multiplexing in optical fibers, time-domain terahertz spectroscopy, ultrafast optics.
2) We will exploit spin-orbit quantum correlations generated within single photons and/or among few correlated photons to demonstrate novel quantum-information protocols using both the polarization and the transverse modes to encode and manipulate multiple qubits in each photon and for the implementation of quantum simulations of material systems based on photonic quantum walks in the Hilbert space of the light transverse modes.
3) We will investigate novel or unexplained physical processes occurring in structured optical media and light-sensitive material systems which respond both to the optical polarization and to its spatial inhomogeneity. Such materials will then be used to manipulate and characterize spin-orbit vector states of light.
Max ERC Funding
1 680 833 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym RARE
Project Dipolar Physics and Rydberg Atoms with Rare-Earth Elements
Researcher (PI) Francesca Ferlaino
Host Institution (HI) UNIVERSITAET INNSBRUCK
Call Details Consolidator Grant (CoG), PE2, ERC-2015-CoG
Summary Strongly magnetic rare-earth atoms are fantastic species to study few- and many-body dipolar quantum physics with ultracold gases. Their appeal leans on their spectacular properties (many stable isotopes, large dipole moment, unconventional interactions, and a rich atomic spectrum). In 2012 my group created the first Bose-Einstein condensate of erbium and shortly thereafter the first degenerate Fermi gas. My pioneering studies, together with the result on dysprosium by the Lev´s group, have triggered an intense research activity in our community on these exotic species.
The RARE project aims at converting complexity into opportunity by exploiting the newly emerged opportunity provided by magnetic rare-earth atoms to access fascinating, yet rather unexplored, quantum regimes. It roots into two innate properties of magnetic lanthanides, namely their large and permanent magnetic dipole moment, and their many valence electrons. With these properties in mind, my proposal targets to obtain groundbreaking insights into dipolar quantum physics and multi-electron ultracold Rydberg gasses:
1) Realization of the first dipolar quantum mixtures, by combining Er and Dy. With this powerful system, we aim to study exotic states of matter under the influence of the strong anisotropic and long-range dipole-dipole interaction, such as anisotropic Cooper pairing and superfluidity, and weakly-bound polar ErDy molecules.
2) Study of non-polarized dipoles at zero and ultra-weak polarizing (magnetic) fields, where the atomic dipole are free to orient. In this special setting, we plan to demonstrate new quantum phases, such as spin-orbit coupled, spinor, and nematic phases.
3) Creation of multi-electron ultracold Rydberg gases, in which the Rydberg and core electrons can be separately controlled and manipulated.
This innovative project goes far beyond the state of the art and promises to capture truly new scientific horizons of quantum physics with ultracold atoms.
for later
Summary
Strongly magnetic rare-earth atoms are fantastic species to study few- and many-body dipolar quantum physics with ultracold gases. Their appeal leans on their spectacular properties (many stable isotopes, large dipole moment, unconventional interactions, and a rich atomic spectrum). In 2012 my group created the first Bose-Einstein condensate of erbium and shortly thereafter the first degenerate Fermi gas. My pioneering studies, together with the result on dysprosium by the Lev´s group, have triggered an intense research activity in our community on these exotic species.
The RARE project aims at converting complexity into opportunity by exploiting the newly emerged opportunity provided by magnetic rare-earth atoms to access fascinating, yet rather unexplored, quantum regimes. It roots into two innate properties of magnetic lanthanides, namely their large and permanent magnetic dipole moment, and their many valence electrons. With these properties in mind, my proposal targets to obtain groundbreaking insights into dipolar quantum physics and multi-electron ultracold Rydberg gasses:
1) Realization of the first dipolar quantum mixtures, by combining Er and Dy. With this powerful system, we aim to study exotic states of matter under the influence of the strong anisotropic and long-range dipole-dipole interaction, such as anisotropic Cooper pairing and superfluidity, and weakly-bound polar ErDy molecules.
2) Study of non-polarized dipoles at zero and ultra-weak polarizing (magnetic) fields, where the atomic dipole are free to orient. In this special setting, we plan to demonstrate new quantum phases, such as spin-orbit coupled, spinor, and nematic phases.
3) Creation of multi-electron ultracold Rydberg gases, in which the Rydberg and core electrons can be separately controlled and manipulated.
This innovative project goes far beyond the state of the art and promises to capture truly new scientific horizons of quantum physics with ultracold atoms.
for later
Max ERC Funding
1 992 368 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym SINCHAIS
Project In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behavior
Researcher (PI) Ryuichi Shigemoto
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Advanced Grant (AdG), LS5, ERC-2015-AdG
Summary Ligand-gated and voltage-gated channels are key molecules in transforming chemical signals into electrical ones and electrical signals into chemical ones, respectively. At excitatory synaptic connections in the brain, activation of AMPA- and NMDA-type glutamate receptors elicits inward currents at the postsynaptic sites, and activation of voltage-gated calcium channels triggers vesicle release of glutamate in the presynaptic sites. Plastic changes in their number, location and property can lead to potentiation or depression of synaptic efficacy, alteration in time course, and coupling to effectors at both postsynaptic and presynaptic sites. These channels are all composed of distinct subunits and their compositions affect channel properties, trafficking to the synaptic sites, and interaction with associated molecules, creating a large diversity of synaptic functions. Although channels with different subunit compositions have been investigated using biochemical and electrophysiological detection methods, very little is known about single channel subunit composition in situ because of the lack of high resolution methods for analysis of protein complex in intact tissues. In this project, I will develop novel technologies to visualize subunit composition at the single channel level in individual synapses by electron microscopy, combining new EM tags, freeze-fracture replica labelling, and electron tomography. Synaptic plasticity will be induced by optogenetic stimulation of identified neurons or behavioural paradigms to examine the dynamic changes of subunit composition. Finally, physiological implications of such regulation of subunit composition will be investigated by genetic manipulation of mice combined with electrophysiological and behavioural analyses. This work will demonstrate unprecedented views of the subunit composition in situ and provide new insights into how regulation of subunit composition contributes to synaptic plasticity and animal behaviour.
Summary
Ligand-gated and voltage-gated channels are key molecules in transforming chemical signals into electrical ones and electrical signals into chemical ones, respectively. At excitatory synaptic connections in the brain, activation of AMPA- and NMDA-type glutamate receptors elicits inward currents at the postsynaptic sites, and activation of voltage-gated calcium channels triggers vesicle release of glutamate in the presynaptic sites. Plastic changes in their number, location and property can lead to potentiation or depression of synaptic efficacy, alteration in time course, and coupling to effectors at both postsynaptic and presynaptic sites. These channels are all composed of distinct subunits and their compositions affect channel properties, trafficking to the synaptic sites, and interaction with associated molecules, creating a large diversity of synaptic functions. Although channels with different subunit compositions have been investigated using biochemical and electrophysiological detection methods, very little is known about single channel subunit composition in situ because of the lack of high resolution methods for analysis of protein complex in intact tissues. In this project, I will develop novel technologies to visualize subunit composition at the single channel level in individual synapses by electron microscopy, combining new EM tags, freeze-fracture replica labelling, and electron tomography. Synaptic plasticity will be induced by optogenetic stimulation of identified neurons or behavioural paradigms to examine the dynamic changes of subunit composition. Finally, physiological implications of such regulation of subunit composition will be investigated by genetic manipulation of mice combined with electrophysiological and behavioural analyses. This work will demonstrate unprecedented views of the subunit composition in situ and provide new insights into how regulation of subunit composition contributes to synaptic plasticity and animal behaviour.
Max ERC Funding
2 481 437 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym TOPSIM
Project Topology and symmetries in synthetic fermionic systems
Researcher (PI) Leonardo Fallani
Host Institution (HI) UNIVERSITA DEGLI STUDI DI FIRENZE
Call Details Consolidator Grant (CoG), PE2, ERC-2015-CoG
Summary Topology and symmetry are two fundamental and intertwined concepts driving the behavior of fermionic systems in both condensed-matter and high-energy physics. The goal of the TOPSIM project is to address open problems concerning topological states of fermionic matter from an experimental point of view, by taking advantage of novel possibilities of quantum control on synthetic systems formed by ultracold neutral atoms. We will investigate the behavior of fermionic matter under strong gauge fields in order to study quantum Hall physics and the emergence of topological order in a fully tunable experimental geometry. We will also synthesize fermionic systems exhibiting enlarged interaction symmetries beyond the SU(2) symmetry of electrons, which will allow us to experimentally realize, for the first time, SU(N) models that have no other experimental counterpart in physics, and to use them to study the emergence of long-sought topological states of matter. With these ambitious goals, the TOPSIM project will considerably advance our understanding of topological fermionic matter, paving the way to new methods of investigation of open questions in both high- and low-energy physics, by approaching many-body problems with metrological quantum control.
Summary
Topology and symmetry are two fundamental and intertwined concepts driving the behavior of fermionic systems in both condensed-matter and high-energy physics. The goal of the TOPSIM project is to address open problems concerning topological states of fermionic matter from an experimental point of view, by taking advantage of novel possibilities of quantum control on synthetic systems formed by ultracold neutral atoms. We will investigate the behavior of fermionic matter under strong gauge fields in order to study quantum Hall physics and the emergence of topological order in a fully tunable experimental geometry. We will also synthesize fermionic systems exhibiting enlarged interaction symmetries beyond the SU(2) symmetry of electrons, which will allow us to experimentally realize, for the first time, SU(N) models that have no other experimental counterpart in physics, and to use them to study the emergence of long-sought topological states of matter. With these ambitious goals, the TOPSIM project will considerably advance our understanding of topological fermionic matter, paving the way to new methods of investigation of open questions in both high- and low-energy physics, by approaching many-body problems with metrological quantum control.
Max ERC Funding
1 595 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym VISONby3DSTIM
Project Restoration of visual perception by artificial stimulation performed by 3D EAO microscopy
Researcher (PI) Jozsef Balázs Rózsa
Host Institution (HI) INSTITUTE OF EXPERIMENTAL MEDICINE - HUNGARIAN ACADEMY OF SCIENCES
Call Details Consolidator Grant (CoG), LS5, ERC-2015-CoG
Summary The long-term aim of the investigation is to assess the feasibility of creating an “artificial sense” and, thereby, a possible sensory (visual) prosthetic. While working towards this goal, we will have to address the question of how neural assembly activity relates to subjective perceptions. Finding and understanding these functional assemblies will make it possible to reactivate them in a precise, biologically relevant manner to elicit similar cortical activation as visual stimulation. Recent publications suggest that cortical connectivity can be mapped by two-photon microscopy. Here we want, therefore, to develop a novel 3D Electro-Acousto-Optical microscope for high-throughput assembly mapping. The microscope will be capable of scanning neuronal activity with one order of magnitude higher speed (300-500 kHz/ROI) and simultaneously photoactivate neurons with three order of magnitude higher efficiency (2,500 – 25,000 neurons/ms) than existing 3D microscopes while preserving the subcellular resolution required to simultaneously measure the somatic, the dendritic and axonal computation units in the entire V1 region of the cortex. The microscope will be based on our current 3D AO technology; on novel ultra-fast scanning technologies; new, 10-fold faster AO deflectors; and novel (multi-ROI) scanning strategies. Using our microscope in combination with novel caged neurotransmitters and optogenetic tools, we want to map cell assemblies and to understand how they form larger clusters and how they are associated with visual features. Furthermore, as a proof-of-concept of this grant, we want to restore visual perception by recreating previously mapped assembly patterns with 3D artificial photositmulation in behaving mice and see if the animal responds to the artificial stimulus in the same way as to the visual stimulus. Moreover, we want to restore visual information based spatial navigation in head restrained animals orienting and moving in a virtual labyrinth for reward.
Summary
The long-term aim of the investigation is to assess the feasibility of creating an “artificial sense” and, thereby, a possible sensory (visual) prosthetic. While working towards this goal, we will have to address the question of how neural assembly activity relates to subjective perceptions. Finding and understanding these functional assemblies will make it possible to reactivate them in a precise, biologically relevant manner to elicit similar cortical activation as visual stimulation. Recent publications suggest that cortical connectivity can be mapped by two-photon microscopy. Here we want, therefore, to develop a novel 3D Electro-Acousto-Optical microscope for high-throughput assembly mapping. The microscope will be capable of scanning neuronal activity with one order of magnitude higher speed (300-500 kHz/ROI) and simultaneously photoactivate neurons with three order of magnitude higher efficiency (2,500 – 25,000 neurons/ms) than existing 3D microscopes while preserving the subcellular resolution required to simultaneously measure the somatic, the dendritic and axonal computation units in the entire V1 region of the cortex. The microscope will be based on our current 3D AO technology; on novel ultra-fast scanning technologies; new, 10-fold faster AO deflectors; and novel (multi-ROI) scanning strategies. Using our microscope in combination with novel caged neurotransmitters and optogenetic tools, we want to map cell assemblies and to understand how they form larger clusters and how they are associated with visual features. Furthermore, as a proof-of-concept of this grant, we want to restore visual perception by recreating previously mapped assembly patterns with 3D artificial photositmulation in behaving mice and see if the animal responds to the artificial stimulus in the same way as to the visual stimulus. Moreover, we want to restore visual information based spatial navigation in head restrained animals orienting and moving in a virtual labyrinth for reward.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-05-01, End date: 2021-04-30