Project acronym CELLTYPESANDCIRCUITS
Project Neural circuit function in the retina of mice and humans
Researcher (PI) Botond Roska
Host Institution (HI) FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary The mammalian brain is assembled from thousands of neuronal cell types that are organized into distinct circuits to perform behaviourally relevant computations. To gain mechanistic insights about brain function and to treat specific diseases of the nervous system it is crucial to understand what these local circuits are computing and how they achieve these computations. By examining the structure and function of a few genetically identified and experimentally accessible neural circuits we plan to address fundamental questions about the functional architecture of neural circuits. First, are cell types assigned to a unique functional circuit with a well-defined function or do they participate in multiple circuits (multitasking cell types), adjusting their role depending on the state of these circuits? Second, does a neural circuit perform a single computation or depending on the information content of its inputs can it carry out radically different functions? Third, how, among the large number of other cell types, do the cells belonging to the same functional circuit connect together during development? We use the mouse retina as a model system to address these questions. Finally, we will study the structure and function of a specialised neural circuit in the human fovea that enables humans to read. We predict that our insights into the mechanism of multitasking, network switches and the development of selective connectivity will be instructive to study similar phenomena in other brain circuits. Knowledge of the structure and function of the human fovea will open up new opportunities to correlate human retinal function with human visual behaviour and our genetic technologies to study human foveal function will allow us and others to design better strategies for restoring vision for the blind.
Summary
The mammalian brain is assembled from thousands of neuronal cell types that are organized into distinct circuits to perform behaviourally relevant computations. To gain mechanistic insights about brain function and to treat specific diseases of the nervous system it is crucial to understand what these local circuits are computing and how they achieve these computations. By examining the structure and function of a few genetically identified and experimentally accessible neural circuits we plan to address fundamental questions about the functional architecture of neural circuits. First, are cell types assigned to a unique functional circuit with a well-defined function or do they participate in multiple circuits (multitasking cell types), adjusting their role depending on the state of these circuits? Second, does a neural circuit perform a single computation or depending on the information content of its inputs can it carry out radically different functions? Third, how, among the large number of other cell types, do the cells belonging to the same functional circuit connect together during development? We use the mouse retina as a model system to address these questions. Finally, we will study the structure and function of a specialised neural circuit in the human fovea that enables humans to read. We predict that our insights into the mechanism of multitasking, network switches and the development of selective connectivity will be instructive to study similar phenomena in other brain circuits. Knowledge of the structure and function of the human fovea will open up new opportunities to correlate human retinal function with human visual behaviour and our genetic technologies to study human foveal function will allow us and others to design better strategies for restoring vision for the blind.
Max ERC Funding
1 499 000 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym COMPUSLANG
Project Neural and computational determinants of left cerebral dominance in speech and language
Researcher (PI) Anne-Lise Mamessier
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary More than a century after Wernicke and Broca established that speech perception and production rely on temporal and prefrontal cortices of the left brain hemisphere, the biological determinants for this organization are still unknown. While functional neuroanatomy has been described in great detail, the neuroscience of language still lacks a physiologically plausible model of the neuro-computational mechanisms for coding and decoding of speech acoustic signal. We propose to fill this gap by testing the biological validity and exploring the computational implications of one promising proposal, the Asymmetric Sampling in Time theory. AST assumes that speech signals are analysed in parallel at multiple timescales and that these timescales differ between left and right cerebral hemispheres. This theory is original and provocative as it implies that a single computational difference, distinct integration windows in right and left auditory cortices could be sufficient to explain why speech is preferentially processed by the left brain, and possible even why the human brain has evolved toward such an asymmetric functional organization. Our proposal has four goals: 1/ to validate, invalidate or amend AST on the basis of physiological experiments in healthy human subjects including functional magnetic resonance imaging (fMRI), combined electroencephalography (EEG) and fMRI, magnetoencephalography (MEG) and subdural electrocorticography (EcoG), 2/ to use computational modeling to probe those aspects of the theory that currently remain inaccessible to empirical testing (evaluation, assessment), 3/ to apply AST to binaural artificial hearing with cochlear implants, 4/ to test for disorders of auditory sampling in autism and dyslexia, two language neurodevelopmental pathologies in which a genetic basis implicates the physiological underpinnings of AST, and 5/ to assess potential generalisation of AST to linguistic action in the context of speech production.
Summary
More than a century after Wernicke and Broca established that speech perception and production rely on temporal and prefrontal cortices of the left brain hemisphere, the biological determinants for this organization are still unknown. While functional neuroanatomy has been described in great detail, the neuroscience of language still lacks a physiologically plausible model of the neuro-computational mechanisms for coding and decoding of speech acoustic signal. We propose to fill this gap by testing the biological validity and exploring the computational implications of one promising proposal, the Asymmetric Sampling in Time theory. AST assumes that speech signals are analysed in parallel at multiple timescales and that these timescales differ between left and right cerebral hemispheres. This theory is original and provocative as it implies that a single computational difference, distinct integration windows in right and left auditory cortices could be sufficient to explain why speech is preferentially processed by the left brain, and possible even why the human brain has evolved toward such an asymmetric functional organization. Our proposal has four goals: 1/ to validate, invalidate or amend AST on the basis of physiological experiments in healthy human subjects including functional magnetic resonance imaging (fMRI), combined electroencephalography (EEG) and fMRI, magnetoencephalography (MEG) and subdural electrocorticography (EcoG), 2/ to use computational modeling to probe those aspects of the theory that currently remain inaccessible to empirical testing (evaluation, assessment), 3/ to apply AST to binaural artificial hearing with cochlear implants, 4/ to test for disorders of auditory sampling in autism and dyslexia, two language neurodevelopmental pathologies in which a genetic basis implicates the physiological underpinnings of AST, and 5/ to assess potential generalisation of AST to linguistic action in the context of speech production.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-02-01, End date: 2016-01-31
Project acronym INTERGENADAPT
Project The interaction and the genetic basis of naturally versus sexually selected traits in the adaptive radiations of cichlid fishes
Researcher (PI) Walter Salzburger
Host Institution (HI) UNIVERSITAT BASEL
Call Details Starting Grant (StG), LS5, ERC-2007-StG
Summary The question of how variation in the DNA translates into organismal diversity has puzzled biologists for decades. Despite of recent advances in evolutionary and developmental biology, the molecular mechanisms that underlie diversification, adaptation and evolutionary innovation remain largely unknown. The exceptionally diverse species flocks of cichlid fishes in the East African Great Lakes are textbook examples for adaptive radiations, and emerge as excellent model systems to study the genetic basis of biodiversity. East Africa’s hundreds of endemic cichlid species are akin a natural mutagenesis screen and differ greatly in ecologically relevant and, hence, naturally selected characters such as mouth morphology, but also in sexually selected traits such as coloration. Here, I propose to study the relative adaptive relevance and the molecular basis of characters that contributed to the origin of the cichlids’ astonishing species-richness, making the underlying genetic pathways prime targets in the quest of “speciation genes”. Specifically, I aim to focus on three unique characters of cichlids: (i) thick lips that evolved independently in different cichlid assemblages; (ii) the highly adaptable pharyngeal jaw apparatus; and (iii) egg-dummies on the anal fins of male haplochromines, which play an important role in the breeding cycle of these mouthbrooding fishes. A major goal of this project is to test whether the same developmental and genetic pathways are involved in the origin of evolutionary parallelisms in cichlid radiations. To this end, I will use gene expression, RT-PCR and in situ hybridization experiments to compare thick-lipped species, parallel pharyngeal jaw morphologies and similar color patterns on fins of cichlids of different assemblages, as well as the egg-spots of haplochromines to those of unrelated ectodine cichlids, in which similar dummies have evolved independently and on a different fin. Finally, I intend to compare the genes underlying these characters in an evolutionary genomic framework in order to evaluate the relative strength and the type of selection that has acted on loci involved in the morphogenesis of naturally versus sexually selected traits in cichlid adaptive radiations.
Summary
The question of how variation in the DNA translates into organismal diversity has puzzled biologists for decades. Despite of recent advances in evolutionary and developmental biology, the molecular mechanisms that underlie diversification, adaptation and evolutionary innovation remain largely unknown. The exceptionally diverse species flocks of cichlid fishes in the East African Great Lakes are textbook examples for adaptive radiations, and emerge as excellent model systems to study the genetic basis of biodiversity. East Africa’s hundreds of endemic cichlid species are akin a natural mutagenesis screen and differ greatly in ecologically relevant and, hence, naturally selected characters such as mouth morphology, but also in sexually selected traits such as coloration. Here, I propose to study the relative adaptive relevance and the molecular basis of characters that contributed to the origin of the cichlids’ astonishing species-richness, making the underlying genetic pathways prime targets in the quest of “speciation genes”. Specifically, I aim to focus on three unique characters of cichlids: (i) thick lips that evolved independently in different cichlid assemblages; (ii) the highly adaptable pharyngeal jaw apparatus; and (iii) egg-dummies on the anal fins of male haplochromines, which play an important role in the breeding cycle of these mouthbrooding fishes. A major goal of this project is to test whether the same developmental and genetic pathways are involved in the origin of evolutionary parallelisms in cichlid radiations. To this end, I will use gene expression, RT-PCR and in situ hybridization experiments to compare thick-lipped species, parallel pharyngeal jaw morphologies and similar color patterns on fins of cichlids of different assemblages, as well as the egg-spots of haplochromines to those of unrelated ectodine cichlids, in which similar dummies have evolved independently and on a different fin. Finally, I intend to compare the genes underlying these characters in an evolutionary genomic framework in order to evaluate the relative strength and the type of selection that has acted on loci involved in the morphogenesis of naturally versus sexually selected traits in cichlid adaptive radiations.
Max ERC Funding
750 000 €
Duration
Start date: 2008-08-01, End date: 2013-07-31
Project acronym WALK AGAIN
Project Multi-pronged Strategies to Regain Voluntary Motor Functions after Spinal Cord Injury
Researcher (PI) Grégoire Richard Courtine
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary Severe spinal cord injury (SCI) permanently abolishes motor functions caudal to the lesion. Various strategies have been
pursued to promote functional recovery after such injuries. However, none of these attempts were able to return voluntary
movements in paralyzed subjects. Here, we propose an innovative transdisciplinary research program including parallel
approaches that will converge into an integrated multi-pronged therapy able to restore voluntary movements after paralyzing
SCI. To achieve this goal, we will capitalize on our recent breakthroughs that demonstrate the impressive capacity of
pharmacological and electrical spinal cord stimulations to promote full weight bearing walking in paralyzed rats when
combined with rehabilitation. In Walk Again, we will improve high level control of spinal circuits with synergistic combinations
of pharmacological agents, and with the design of multisite stimulation strategies using electrode arrays. Functional electrical
stimulation of muscles will provide complementary low level tuning capacities to adjust limb motion. To allow voluntary control,
we will establish a new line of research and pioneer brain-spinal interfaces by which cortical modulations will directly adjust
stimulations of spinal circuits and muscles. In the final stages, we will enable neurorehabilitation with this cortico-spinal
neuroprosthesis in the presence of anti-NogoA regenerative therapy. The underlying objective is to devise a fully-operative
neuroprosthetic system that will enable self-driven rehabilitation in a permissive plastic environment. Walk Again will fertilize
frontier research with pioneer ideas that will increase European competitiveness while paving the way toward viable clinical
applications to restore function in paralyzed individuals.
Summary
Severe spinal cord injury (SCI) permanently abolishes motor functions caudal to the lesion. Various strategies have been
pursued to promote functional recovery after such injuries. However, none of these attempts were able to return voluntary
movements in paralyzed subjects. Here, we propose an innovative transdisciplinary research program including parallel
approaches that will converge into an integrated multi-pronged therapy able to restore voluntary movements after paralyzing
SCI. To achieve this goal, we will capitalize on our recent breakthroughs that demonstrate the impressive capacity of
pharmacological and electrical spinal cord stimulations to promote full weight bearing walking in paralyzed rats when
combined with rehabilitation. In Walk Again, we will improve high level control of spinal circuits with synergistic combinations
of pharmacological agents, and with the design of multisite stimulation strategies using electrode arrays. Functional electrical
stimulation of muscles will provide complementary low level tuning capacities to adjust limb motion. To allow voluntary control,
we will establish a new line of research and pioneer brain-spinal interfaces by which cortical modulations will directly adjust
stimulations of spinal circuits and muscles. In the final stages, we will enable neurorehabilitation with this cortico-spinal
neuroprosthesis in the presence of anti-NogoA regenerative therapy. The underlying objective is to devise a fully-operative
neuroprosthetic system that will enable self-driven rehabilitation in a permissive plastic environment. Walk Again will fertilize
frontier research with pioneer ideas that will increase European competitiveness while paving the way toward viable clinical
applications to restore function in paralyzed individuals.
Max ERC Funding
1 395 540 €
Duration
Start date: 2010-12-01, End date: 2015-11-30
