Project acronym 5HT-OPTOGENETICS
Project Optogenetic Analysis of Serotonin Function in the Mammalian Brain
Researcher (PI) Zachary Mainen
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.
Summary
Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.
Max ERC Funding
2 318 636 €
Duration
Start date: 2010-07-01, End date: 2015-12-31
Project acronym 5HTCircuits
Project Modulation of cortical circuits and predictive neural coding by serotonin
Researcher (PI) Zachary Mainen
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Advanced Grant (AdG), LS5, ERC-2014-ADG
Summary Serotonin (5-HT) is a central neuromodulator and a major target of therapeutic psychoactive drugs, but relatively little is known about how it modulates information processing in neural circuits. The theory of predictive coding postulates that the brain combines raw bottom-up sensory information with top-down information from internal models to make perceptual inferences about the world. We hypothesize, based on preliminary data and prior literature, that a role of 5-HT in this process is to report prediction errors and promote the suppression and weakening of erroneous internal models. We propose that it does this by inhibiting top-down relative to bottom-up cortical information flow. To test this hypothesis, we propose a set of experiments in mice performing olfactory perceptual tasks. Our specific aims are: (1) We will test whether 5-HT neurons encode sensory prediction errors. (2) We will test their causal role in using predictive cues to guide perceptual decisions. (3) We will characterize how 5-HT influences the encoding of sensory information by neuronal populations in the olfactory cortex and identify the underlying circuitry. (4) Finally, we will map the effects of 5-HT across the whole brain and use this information to target further causal manipulations to specific 5-HT projections. We accomplish these aims using state-of-the-art optogenetic, electrophysiological and imaging techniques (including 9.4T small-animal functional magnetic resonance imaging) as well as psychophysical tasks amenable to quantitative analysis and computational theory. Together, these experiments will tackle multiple facets of an important general computational question, bringing to bear an array of cutting-edge technologies to address with unprecedented mechanistic detail how 5-HT impacts neural coding and perceptual decision-making.
Summary
Serotonin (5-HT) is a central neuromodulator and a major target of therapeutic psychoactive drugs, but relatively little is known about how it modulates information processing in neural circuits. The theory of predictive coding postulates that the brain combines raw bottom-up sensory information with top-down information from internal models to make perceptual inferences about the world. We hypothesize, based on preliminary data and prior literature, that a role of 5-HT in this process is to report prediction errors and promote the suppression and weakening of erroneous internal models. We propose that it does this by inhibiting top-down relative to bottom-up cortical information flow. To test this hypothesis, we propose a set of experiments in mice performing olfactory perceptual tasks. Our specific aims are: (1) We will test whether 5-HT neurons encode sensory prediction errors. (2) We will test their causal role in using predictive cues to guide perceptual decisions. (3) We will characterize how 5-HT influences the encoding of sensory information by neuronal populations in the olfactory cortex and identify the underlying circuitry. (4) Finally, we will map the effects of 5-HT across the whole brain and use this information to target further causal manipulations to specific 5-HT projections. We accomplish these aims using state-of-the-art optogenetic, electrophysiological and imaging techniques (including 9.4T small-animal functional magnetic resonance imaging) as well as psychophysical tasks amenable to quantitative analysis and computational theory. Together, these experiments will tackle multiple facets of an important general computational question, bringing to bear an array of cutting-edge technologies to address with unprecedented mechanistic detail how 5-HT impacts neural coding and perceptual decision-making.
Max ERC Funding
2 486 074 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym A-FRO
Project Actively Frozen - contextual modulation of freezing and its neuronal basis
Researcher (PI) Marta de Aragão Pacheco Moita
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Consolidator Grant (CoG), LS5, ERC-2018-COG
Summary When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.
Summary
When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.
Max ERC Funding
1 969 750 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym activeFly
Project Circuit mechanisms of self-movement estimation during walking
Researcher (PI) M Eugenia CHIAPPE
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Starting Grant (StG), LS5, ERC-2017-STG
Summary The brain evolves, develops, and operates in the context of animal movements. As a consequence, fundamental brain functions such as spatial perception and motor control critically depend on the precise knowledge of the ongoing body motion. An accurate internal estimate of self-movement is thought to emerge from sensorimotor integration; nonetheless, which circuits perform this internal estimation, and exactly how motor-sensory coordination is implemented within these circuits are basic questions that remain to be poorly understood. There is growing evidence suggesting that, during locomotion, motor-related and visual signals interact at early stages of visual processing. In mammals, however, it is not clear what the function of this interaction is. Recently, we have shown that a population of Drosophila optic-flow processing neurons —neurons that are sensitive to self-generated visual flow, receives convergent visual and walking-related signals to form a faithful representation of the fly’s walking movements. Leveraging from these results, and combining quantitative analysis of behavior with physiology, optogenetics, and modelling, we propose to investigate circuit mechanisms of self-movement estimation during walking. We will:1) use cell specific manipulations to identify what cells are necessary to generate the motor-related activity in the population of visual neurons, 2) record from the identified neurons and correlate their activity with specific locomotor parameters, and 3) perturb the activity of different cell-types within the identified circuits to test their role in the dynamics of the visual neurons, and on the fly’s walking behavior. These experiments will establish unprecedented causal relationships among neural activity, the formation of an internal representation, and locomotor control. The identified sensorimotor principles will establish a framework that can be tested in other scenarios or animal systems with implications both in health and disease.
Summary
The brain evolves, develops, and operates in the context of animal movements. As a consequence, fundamental brain functions such as spatial perception and motor control critically depend on the precise knowledge of the ongoing body motion. An accurate internal estimate of self-movement is thought to emerge from sensorimotor integration; nonetheless, which circuits perform this internal estimation, and exactly how motor-sensory coordination is implemented within these circuits are basic questions that remain to be poorly understood. There is growing evidence suggesting that, during locomotion, motor-related and visual signals interact at early stages of visual processing. In mammals, however, it is not clear what the function of this interaction is. Recently, we have shown that a population of Drosophila optic-flow processing neurons —neurons that are sensitive to self-generated visual flow, receives convergent visual and walking-related signals to form a faithful representation of the fly’s walking movements. Leveraging from these results, and combining quantitative analysis of behavior with physiology, optogenetics, and modelling, we propose to investigate circuit mechanisms of self-movement estimation during walking. We will:1) use cell specific manipulations to identify what cells are necessary to generate the motor-related activity in the population of visual neurons, 2) record from the identified neurons and correlate their activity with specific locomotor parameters, and 3) perturb the activity of different cell-types within the identified circuits to test their role in the dynamics of the visual neurons, and on the fly’s walking behavior. These experiments will establish unprecedented causal relationships among neural activity, the formation of an internal representation, and locomotor control. The identified sensorimotor principles will establish a framework that can be tested in other scenarios or animal systems with implications both in health and disease.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-11-01, End date: 2022-10-31
Project acronym C.o.C.O.
Project Circuits of con-specific observation
Researcher (PI) Marta De Aragao Pacheco Moita
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Starting Grant (StG), LS5, ERC-2013-StG
Summary A great deal is known about the neural basis of associative fear learning. However, many animal species are able to use social cues to recognize threats, a defence mechanism that may be less costly than learning from self-experience. We have previously shown that rats perceive the cessation of movement-evoked sound as a signal of danger and its resumption as a signal of safety. To study transmission of fear between rats we assessed the behavior of an observer while witnessing a demonstrator rat display fear responses. With this paradigm we will take advantage of the accumulated knowledge on learned fear to investigate the neural mechanisms by which the social environment regulates defense behaviors. We will unravel the neural circuits involved in detecting the transition from movement-evoked sound to silence. Moreover, since observer rats previously exposed to shock display observational freezing, but naive observer rats do not, we will determine the mechanism by which prior experience contribute to observational freezing. To this end, we will focus on the amygdala, crucial for fear learning and expression, and its auditory inputs, combining immunohistochemistry, pharmacology and optogenetics. Finally, as the detection of and responses to threat are often inherently social, we will study these behaviors in the context of large groups of individuals. To circumvent the serious limitations in using large populations of rats, we will resort to a different model system. The fruit fly is the ideal model system, as it is both amenable to the search for the neural mechanism of behavior, while at the same time allowing the study of the behavior of large groups of individuals. We will develop behavioral tasks, where conditioned demonstrator flies signal danger to other naïve ones. These experiments unravel how the brain uses defense behaviors as signals of danger and how it contributes to defense mechanisms at the population level.
Summary
A great deal is known about the neural basis of associative fear learning. However, many animal species are able to use social cues to recognize threats, a defence mechanism that may be less costly than learning from self-experience. We have previously shown that rats perceive the cessation of movement-evoked sound as a signal of danger and its resumption as a signal of safety. To study transmission of fear between rats we assessed the behavior of an observer while witnessing a demonstrator rat display fear responses. With this paradigm we will take advantage of the accumulated knowledge on learned fear to investigate the neural mechanisms by which the social environment regulates defense behaviors. We will unravel the neural circuits involved in detecting the transition from movement-evoked sound to silence. Moreover, since observer rats previously exposed to shock display observational freezing, but naive observer rats do not, we will determine the mechanism by which prior experience contribute to observational freezing. To this end, we will focus on the amygdala, crucial for fear learning and expression, and its auditory inputs, combining immunohistochemistry, pharmacology and optogenetics. Finally, as the detection of and responses to threat are often inherently social, we will study these behaviors in the context of large groups of individuals. To circumvent the serious limitations in using large populations of rats, we will resort to a different model system. The fruit fly is the ideal model system, as it is both amenable to the search for the neural mechanism of behavior, while at the same time allowing the study of the behavior of large groups of individuals. We will develop behavioral tasks, where conditioned demonstrator flies signal danger to other naïve ones. These experiments unravel how the brain uses defense behaviors as signals of danger and how it contributes to defense mechanisms at the population level.
Max ERC Funding
1 412 376 €
Duration
Start date: 2013-12-01, End date: 2018-11-30
Project acronym CHEMOSENSORYCIRCUITS
Project Function of Chemosensory Circuits
Researcher (PI) Emre Yaksi
Host Institution (HI) NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU
Call Details Starting Grant (StG), LS5, ERC-2013-StG
Summary Smell and taste are the least studied of all senses. Very little is known about chemosensory information processing beyond the level of receptor neurons. Every morning we enjoy our coffee thanks to our brains ability to combine and process multiple sensory modalities. Meanwhile, we can still review a document on our desk by adjusting the weights of numerous sensory inputs that constantly bombard our brains. Yet, the smell of our coffee may remind us that pleasant weekend breakfast through associative learning and memory. In the proposed project we will explore the function and the architecture of neural circuits that are involved in olfactory and gustatory information processing, namely habenula and brainstem. Moreover we will investigate the fundamental principles underlying multimodal sensory integration and the neural basis of behavior in these highly conserved brain areas.
To achieve these goals we will take an innovative approach by combining two-photon calcium imaging, optogenetics and electrophysiology with the expanding genetic toolbox of a small vertebrate, the zebrafish. This pioneering approach will enable us to design new types of experiments that were unthinkable only a few years ago. Using this unique combination of methods, we will monitor and perturb the activity of functionally distinct elements of habenular and brainstem circuits, in vivo. The habenula and brainstem are important in mediating stress/anxiety and eating habits respectively. Therefore, understanding the neural computations in these brain regions is important for comprehending the neural mechanisms underlying psychological conditions related to anxiety and eating disorders. We anticipate that our results will go beyond chemical senses and contribute new insights to the understanding of how brain circuits work and interact with the sensory world to shape neural activity and behavioral outputs of animals.
Summary
Smell and taste are the least studied of all senses. Very little is known about chemosensory information processing beyond the level of receptor neurons. Every morning we enjoy our coffee thanks to our brains ability to combine and process multiple sensory modalities. Meanwhile, we can still review a document on our desk by adjusting the weights of numerous sensory inputs that constantly bombard our brains. Yet, the smell of our coffee may remind us that pleasant weekend breakfast through associative learning and memory. In the proposed project we will explore the function and the architecture of neural circuits that are involved in olfactory and gustatory information processing, namely habenula and brainstem. Moreover we will investigate the fundamental principles underlying multimodal sensory integration and the neural basis of behavior in these highly conserved brain areas.
To achieve these goals we will take an innovative approach by combining two-photon calcium imaging, optogenetics and electrophysiology with the expanding genetic toolbox of a small vertebrate, the zebrafish. This pioneering approach will enable us to design new types of experiments that were unthinkable only a few years ago. Using this unique combination of methods, we will monitor and perturb the activity of functionally distinct elements of habenular and brainstem circuits, in vivo. The habenula and brainstem are important in mediating stress/anxiety and eating habits respectively. Therefore, understanding the neural computations in these brain regions is important for comprehending the neural mechanisms underlying psychological conditions related to anxiety and eating disorders. We anticipate that our results will go beyond chemical senses and contribute new insights to the understanding of how brain circuits work and interact with the sensory world to shape neural activity and behavioral outputs of animals.
Max ERC Funding
1 499 471 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym CIRCUIT
Project Neural circuits for space representation in the mammalian cortex
Researcher (PI) Edvard Ingjald Moser
Host Institution (HI) NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU
Call Details Advanced Grant (AdG), LS5, ERC-2008-AdG
Summary Neuroscience is one of the fastest-developing areas of science, but it is fair to say that we are still far from understanding how the brain produces subjective experience. For example, simple questions about the origin of thought, imagination, social interaction, or feelings lack even rudimentary answers. We have learnt much about the workings of individual cells and synapses, but psychological phenomena cannot be understood only at this level. These phenomena all emerge from interactions between large numbers of diverse cells in intermingled neural circuits. A major obstacle has been the absence of concepts and tools for investigating neural computation at the circuit level. The aim of this proposal is to combine new transgenic methods for cell type-specific intervention with large-scale multisite single-cell recording to determine how a basic cognitive function self-localization is generated in a functionally well-described mammalian neural circuit. We shall use our recent discovery of entorhinal grid cells as an access ramp. Grid cells fire only when the animal moves through certain locations. For each cell, these locations define a periodic triangular array spanning the whole environment. Grid cells co-exist with other entorhinal cell types encoding head direction, geometric borders, or conjunctions of features. This network is thought to form an essential part of the brain s coordinate system for metric navigation but the detailed wiring, the mechanism of grid formation, and the function of each morphological and functional cell type all remain to be determined. We shall address these open questions by measuring how dynamic spatial representation is affected by transgene-induced activation or inactivation of the individual components of the circuit. The endeavour will pioneer the functional analysis of neural circuits and may, perhaps for the first time, provide us with mechanistic insight into a non-sensory cognitive function in the mammalian cortex.
Summary
Neuroscience is one of the fastest-developing areas of science, but it is fair to say that we are still far from understanding how the brain produces subjective experience. For example, simple questions about the origin of thought, imagination, social interaction, or feelings lack even rudimentary answers. We have learnt much about the workings of individual cells and synapses, but psychological phenomena cannot be understood only at this level. These phenomena all emerge from interactions between large numbers of diverse cells in intermingled neural circuits. A major obstacle has been the absence of concepts and tools for investigating neural computation at the circuit level. The aim of this proposal is to combine new transgenic methods for cell type-specific intervention with large-scale multisite single-cell recording to determine how a basic cognitive function self-localization is generated in a functionally well-described mammalian neural circuit. We shall use our recent discovery of entorhinal grid cells as an access ramp. Grid cells fire only when the animal moves through certain locations. For each cell, these locations define a periodic triangular array spanning the whole environment. Grid cells co-exist with other entorhinal cell types encoding head direction, geometric borders, or conjunctions of features. This network is thought to form an essential part of the brain s coordinate system for metric navigation but the detailed wiring, the mechanism of grid formation, and the function of each morphological and functional cell type all remain to be determined. We shall address these open questions by measuring how dynamic spatial representation is affected by transgene-induced activation or inactivation of the individual components of the circuit. The endeavour will pioneer the functional analysis of neural circuits and may, perhaps for the first time, provide us with mechanistic insight into a non-sensory cognitive function in the mammalian cortex.
Max ERC Funding
2 499 112 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym COGSYSTEMS
Project Understanding actions and intentions of others
Researcher (PI) Giacomo Rizzolatti
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PARMA
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary How do we understand the actions and intentions of others? Hereby we intend to address this issue by using a multidisciplinary approach. Our project is subdivided into four parts. In the first part we investigate the neural organization of monkey area F5, an area deeply involved in motor act understanding. By using a new set of electrodes we will describe the columnar organization of the area F5, establish the temporal relationships between the activity of F5 mirror and motor neurons, and correlate the activity of mirror neurons coding the observed motor acts in peripersonal and extrapersonal space with the activity of motor neurons in the same cortical column. In the second part we will assess the neural mechanism underlying the understanding of the intention of complex actions , i.e. actions formed by a sequence of two (or more) individual actions. The focus will be on the neurons located in ventrolateral prefrontal cortex, an area involved in the organization of high-order motor behavior. The rational of the experiment is that, while the organization of single actions and the understanding of intention behind them is function of parietal neurons, that of complex actions relies on the activity of the prefrontal lobe. In the third and fourth parts of the project we will delimit the cortical areas involved in understanding the goal (the what) and the intention (the why) of the observed actions in individuals with typical development (TD) and in children with autism and will establish the time relation between these two processes. Our hypothesis is that the chained organization of intentional motor acts is impaired in children with autism and this impairment prevents them from organizing normally their actions and from understanding others intentions.
Summary
How do we understand the actions and intentions of others? Hereby we intend to address this issue by using a multidisciplinary approach. Our project is subdivided into four parts. In the first part we investigate the neural organization of monkey area F5, an area deeply involved in motor act understanding. By using a new set of electrodes we will describe the columnar organization of the area F5, establish the temporal relationships between the activity of F5 mirror and motor neurons, and correlate the activity of mirror neurons coding the observed motor acts in peripersonal and extrapersonal space with the activity of motor neurons in the same cortical column. In the second part we will assess the neural mechanism underlying the understanding of the intention of complex actions , i.e. actions formed by a sequence of two (or more) individual actions. The focus will be on the neurons located in ventrolateral prefrontal cortex, an area involved in the organization of high-order motor behavior. The rational of the experiment is that, while the organization of single actions and the understanding of intention behind them is function of parietal neurons, that of complex actions relies on the activity of the prefrontal lobe. In the third and fourth parts of the project we will delimit the cortical areas involved in understanding the goal (the what) and the intention (the why) of the observed actions in individuals with typical development (TD) and in children with autism and will establish the time relation between these two processes. Our hypothesis is that the chained organization of intentional motor acts is impaired in children with autism and this impairment prevents them from organizing normally their actions and from understanding others intentions.
Max ERC Funding
1 992 000 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym CONCEPT
Project Construction of Perception from Touch Signals
Researcher (PI) Mathew Diamond
Host Institution (HI) SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Call Details Advanced Grant (AdG), LS5, ERC-2011-ADG_20110310
Summary Our sensory systems gather stimuli as elemental physical features yet we perceive a world made up of familiar objects, not wavelengths or vibrations. Perception occurs when the neuronal representation of physical parameters is transformed into the neuronal representation of meaningful objects. How does this recoding occur? An ideal platform for the inquiry is the rat whisker sensory system: it produces fast and accurate judgments of complex stimuli, yet can be broken down into accessible neuronal mechanisms. CONCEPT will examine the process that begins with whisker motion and ends with perception of the contacted object. Understanding the general principles for the construction of perception will help explain why we experience the world as we do.
The main hypothesis is that graded neuronal representations at early processing stages are “fractured” to generate discrete object representations at late processing stages. Of particular interest is the emergence of object representations as the meaning of new stimuli is acquired.
We will collect multi-site single-unit and local field potential signals simultaneously with precise behavioral indices, and will interpret data through advanced computational methods. We will begin by quantifying whisker motion as rats discriminate texture, thus defining the raw material on which the brain operates. Next, we will characterize the transformation of texture along an intracortical stream from sensory areas (where we expect that neurons encode whisker kinematics) to frontal and rhinal areas (where we expect that neurons encode objects extracted from the graded physical continuum) and hippocampus (where we expect that neurons encode objects in conjunction with context). We will test candidate processing schemes by manipulating perception on single trials using optogenetic methods.
Summary
Our sensory systems gather stimuli as elemental physical features yet we perceive a world made up of familiar objects, not wavelengths or vibrations. Perception occurs when the neuronal representation of physical parameters is transformed into the neuronal representation of meaningful objects. How does this recoding occur? An ideal platform for the inquiry is the rat whisker sensory system: it produces fast and accurate judgments of complex stimuli, yet can be broken down into accessible neuronal mechanisms. CONCEPT will examine the process that begins with whisker motion and ends with perception of the contacted object. Understanding the general principles for the construction of perception will help explain why we experience the world as we do.
The main hypothesis is that graded neuronal representations at early processing stages are “fractured” to generate discrete object representations at late processing stages. Of particular interest is the emergence of object representations as the meaning of new stimuli is acquired.
We will collect multi-site single-unit and local field potential signals simultaneously with precise behavioral indices, and will interpret data through advanced computational methods. We will begin by quantifying whisker motion as rats discriminate texture, thus defining the raw material on which the brain operates. Next, we will characterize the transformation of texture along an intracortical stream from sensory areas (where we expect that neurons encode whisker kinematics) to frontal and rhinal areas (where we expect that neurons encode objects extracted from the graded physical continuum) and hippocampus (where we expect that neurons encode objects in conjunction with context). We will test candidate processing schemes by manipulating perception on single trials using optogenetic methods.
Max ERC Funding
2 500 000 €
Duration
Start date: 2012-06-01, End date: 2018-05-31
Project acronym DisConn
Project Neural drivers of functional disconnectivity in brain disorders
Researcher (PI) Alessandro GOZZI
Host Institution (HI) FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Call Details Starting Grant (StG), LS5, ERC-2018-STG
Summary A rapidly expanding approach to understanding neural organization is to map patterns of spontaneous neural activity as an index of functional communication and connectivity across brain regions. Fostered by the advent of neuroimaging methods like resting-state fMRI (rsfMRI), this approach has revealed that functional connectivity is almost invariably disrupted in severe psychiatric disorders, such as autism or schizophrenia. However, the neural basis of such functional disconnectivity remains mysterious. What drives brain-wide functional synchronization? And are there shared pathophysiological mechanisms leading to impaired large-scale neural coupling?
This project aims to elucidate the neural drivers of macroscale functional connectivity, as well as its breakdown in brain connectopathies. To achieve this goal, I propose a multi-scale perturbational approach to establish causal relationships between specific neural events and brain-wide functional connectivity via a novel combination of rsfMRI and advanced neural manipulations and recordings in the awake mouse.
By directionally silencing functional hubs as well as more peripheral cortical regions, I will provide a hierarchical description of spontaneous network organization that will uncover regional substrates vulnerable to network disruption. I will also manipulate physiologically-distinct excitatory or inhibitory populations to probe a unifying mechanistic link between excitatory/inhibitory imbalances and aberrant functional connectivity. Finally, to account for the hallmark co-occurrence of synaptic deficits and functional disconnectivity in developmental disorders, I will link cellular mechanisms of synaptic plasticity and learning to the generation of canonical and aberrant spontaneous activity patterns. These studies will pave the way to a back-translation of aberrant functional connectivity into interpretable neurophysiological events and models that can help understand, diagnose or treat brain disorders.
Summary
A rapidly expanding approach to understanding neural organization is to map patterns of spontaneous neural activity as an index of functional communication and connectivity across brain regions. Fostered by the advent of neuroimaging methods like resting-state fMRI (rsfMRI), this approach has revealed that functional connectivity is almost invariably disrupted in severe psychiatric disorders, such as autism or schizophrenia. However, the neural basis of such functional disconnectivity remains mysterious. What drives brain-wide functional synchronization? And are there shared pathophysiological mechanisms leading to impaired large-scale neural coupling?
This project aims to elucidate the neural drivers of macroscale functional connectivity, as well as its breakdown in brain connectopathies. To achieve this goal, I propose a multi-scale perturbational approach to establish causal relationships between specific neural events and brain-wide functional connectivity via a novel combination of rsfMRI and advanced neural manipulations and recordings in the awake mouse.
By directionally silencing functional hubs as well as more peripheral cortical regions, I will provide a hierarchical description of spontaneous network organization that will uncover regional substrates vulnerable to network disruption. I will also manipulate physiologically-distinct excitatory or inhibitory populations to probe a unifying mechanistic link between excitatory/inhibitory imbalances and aberrant functional connectivity. Finally, to account for the hallmark co-occurrence of synaptic deficits and functional disconnectivity in developmental disorders, I will link cellular mechanisms of synaptic plasticity and learning to the generation of canonical and aberrant spontaneous activity patterns. These studies will pave the way to a back-translation of aberrant functional connectivity into interpretable neurophysiological events and models that can help understand, diagnose or treat brain disorders.
Max ERC Funding
1 498 125 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
