Project acronym COGOPTO
Project The role of parvalbumin interneurons in cognition and behavior
Researcher (PI) Eva Marie Carlen
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), LS5, ERC-2013-StG
Summary Cognition is a collective term for complex but sophisticated mental processes such as attention, learning, social interaction, language production, decision making and other executive functions. For normal brain function, these higher-order functions need to be aptly regulated and controlled, and the physiology and cellular substrates for cognitive functions are under intense investigation. The loss of cognitive control is intricately related to pathological states such as schizophrenia, depression, attention deficit hyperactive disorder and addiction.
Synchronized neural activity can be observed when the brain performs several important functions, including cognitive processes. As an example, gamma activity (30-80 Hz) predicts the allocation of attention and theta activity (4-12 Hz) is tightly linked to memory processes. A large body of work indicates that the integrity of local and global neural synchrony is mediated by interneuron networks and actuated by the balance of different neuromodulators.
However, much knowledge is still needed on the functional role interneurons play in cognitive processes, i.e. how the interneurons contribute to local and global network processes subserving cognition, and ultimately play a role in behavior. In addition, we need to understand how neuro-modulators, such as dopamine, regulate interneuron function.
The proposed project aims to functionally determine the specific role the parvalbumin interneurons and the neuromodulator dopamine in aspects of cognition, and in behavior. In addition, we ask the question if cognition can be enhanced.
We are employing a true multidisciplinary approach where brain activity is recorded in conjunctions with optogenetic manipulations of parvalbumin interneurons in animals performing cognitive tasks. In one set of experiments knock-down of dopamine receptors specifically in parvalbumin interneurons is employed to probe how this neuromodulator regulate network functions.
Summary
Cognition is a collective term for complex but sophisticated mental processes such as attention, learning, social interaction, language production, decision making and other executive functions. For normal brain function, these higher-order functions need to be aptly regulated and controlled, and the physiology and cellular substrates for cognitive functions are under intense investigation. The loss of cognitive control is intricately related to pathological states such as schizophrenia, depression, attention deficit hyperactive disorder and addiction.
Synchronized neural activity can be observed when the brain performs several important functions, including cognitive processes. As an example, gamma activity (30-80 Hz) predicts the allocation of attention and theta activity (4-12 Hz) is tightly linked to memory processes. A large body of work indicates that the integrity of local and global neural synchrony is mediated by interneuron networks and actuated by the balance of different neuromodulators.
However, much knowledge is still needed on the functional role interneurons play in cognitive processes, i.e. how the interneurons contribute to local and global network processes subserving cognition, and ultimately play a role in behavior. In addition, we need to understand how neuro-modulators, such as dopamine, regulate interneuron function.
The proposed project aims to functionally determine the specific role the parvalbumin interneurons and the neuromodulator dopamine in aspects of cognition, and in behavior. In addition, we ask the question if cognition can be enhanced.
We are employing a true multidisciplinary approach where brain activity is recorded in conjunctions with optogenetic manipulations of parvalbumin interneurons in animals performing cognitive tasks. In one set of experiments knock-down of dopamine receptors specifically in parvalbumin interneurons is employed to probe how this neuromodulator regulate network functions.
Max ERC Funding
1 400 000 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
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 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 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 ConCorND
Project Connectivity Correlate of Molecular Pathology in Neurodegeneration
Researcher (PI) Smita SAXENA
Host Institution (HI) UNIVERSITAET BERN
Call Details Consolidator Grant (CoG), LS5, ERC-2016-COG
Summary Neurodegenerative diseases (NDs) are incurable, debilitating conditions, arise mid-late in life, represent an enormous health and socioeconomic burden and no therapies exist. An enigmatic finding in NDs is the early and selective alteration in intrinsic excitability of vulnerable neurons paralleling changes in its circuitry. However, a gap in understanding exists in ND field about the cause of these alterations and whether these modifications regulate degenerative pathomechanisms. Our recent study, examining mechanisms of Purkinje cell (PC) degeneration in Spinocerebellar ataxia type 1 (SCA1) revealed that the earliest cerebellar alterations occur in the major excitatory inputs onto PCs, the climbing fibers (CFs). Based on this, we propose a novel three-step model of neurodegeneration: First, suboptimal functioning of the presynaptic inputs initiates signaling deficits in target PCs. Second, those alterations trigger maladaptive responses such as altered intrinsic PC excitability, thus amplifying pathogenic cascades. Third, at network level progressive dysfunction triggers compensatory synaptic modifications within the cerebellar circuitry. In this proposal, we will test our new hypothesis for NDs on SCA1 and this will be the first study to test circuit-dependency in NDs by selectively silencing presynaptic inputs and examining molecular responses in the postsynaptic neuron. Specifically, we will 1) Identify the dysfunctional CF associated molecular signature in PCs. 2) Elucidate mechanisms involved in altering intrinsic PC excitability. 3) Map the connectome for a structural correlate of the pathology. Using conditional mouse models, pharmacogenetics, transcriptomics, proteomics and connectomics, we will delineate molecular alterations that govern disease from compensatory alterations. Our systematic approach will not only impact SCA related therapies but the entire spectrum of NDs and has the potential to change the conceptual approach of future studies on NDs.
Summary
Neurodegenerative diseases (NDs) are incurable, debilitating conditions, arise mid-late in life, represent an enormous health and socioeconomic burden and no therapies exist. An enigmatic finding in NDs is the early and selective alteration in intrinsic excitability of vulnerable neurons paralleling changes in its circuitry. However, a gap in understanding exists in ND field about the cause of these alterations and whether these modifications regulate degenerative pathomechanisms. Our recent study, examining mechanisms of Purkinje cell (PC) degeneration in Spinocerebellar ataxia type 1 (SCA1) revealed that the earliest cerebellar alterations occur in the major excitatory inputs onto PCs, the climbing fibers (CFs). Based on this, we propose a novel three-step model of neurodegeneration: First, suboptimal functioning of the presynaptic inputs initiates signaling deficits in target PCs. Second, those alterations trigger maladaptive responses such as altered intrinsic PC excitability, thus amplifying pathogenic cascades. Third, at network level progressive dysfunction triggers compensatory synaptic modifications within the cerebellar circuitry. In this proposal, we will test our new hypothesis for NDs on SCA1 and this will be the first study to test circuit-dependency in NDs by selectively silencing presynaptic inputs and examining molecular responses in the postsynaptic neuron. Specifically, we will 1) Identify the dysfunctional CF associated molecular signature in PCs. 2) Elucidate mechanisms involved in altering intrinsic PC excitability. 3) Map the connectome for a structural correlate of the pathology. Using conditional mouse models, pharmacogenetics, transcriptomics, proteomics and connectomics, we will delineate molecular alterations that govern disease from compensatory alterations. Our systematic approach will not only impact SCA related therapies but the entire spectrum of NDs and has the potential to change the conceptual approach of future studies on NDs.
Max ERC Funding
2 000 000 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym CoordinatedDopamine
Project Coordination of regional dopamine release in the striatum during habit formation and compulsive behaviour
Researcher (PI) Ingo Willuhn
Host Institution (HI) ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary The basal ganglia consist of a set of neuroanatomical structures that participate in the representation and execution of action sequences. Dopamine neurotransmission in the striatum, the main input nucleus of the basal ganglia, is a fundamental mechanism involved in learning and regulation of such actions. The striatum has multiple functional units, where the limbic striatum is thought to mediate motivational aspects of actions (e.g., goal-directedness) and the sensorimotor striatum their automation (e.g., habit formation). A long-standing question in the field is how limbic and sensorimotor domains communicate with each other, and specifically if they do so during the automation of action sequences. It has been suggested that such coordination is implemented by reciprocal loop connections between striatal projection neurons and the dopaminergic midbrain. Although very influential in theory the effectiveness of this limbic-sensorimotor “bridging” principle has yet to be verified. I hypothesize that during the automation of behaviour regional dopamine signalling is governed by a striatal hierarchy and that dysregulation of this coordination leads to compulsive execution of automatic actions characteristic of several psychiatric disorders. To test this hypothesis, we will conduct electrochemical measurements with real-time resolution simultaneously in limbic and sensorimotor striatum to assess the regional coordination of dopamine release in behaving animals. We developed novel chronically implantable electrodes to enable monitoring of dopamine dynamics throughout the development of habitual behaviour and its compulsive execution in transgenic rats - a species suitable for our complex behavioural assays. Novel rabies virus-mediated gene delivery for in vivo optogenetics in these rats will give us the unique opportunity to test whether specific loop pathways govern striatal dopamine transmission and are causally involved in habit formation and compulsive behaviour.
Summary
The basal ganglia consist of a set of neuroanatomical structures that participate in the representation and execution of action sequences. Dopamine neurotransmission in the striatum, the main input nucleus of the basal ganglia, is a fundamental mechanism involved in learning and regulation of such actions. The striatum has multiple functional units, where the limbic striatum is thought to mediate motivational aspects of actions (e.g., goal-directedness) and the sensorimotor striatum their automation (e.g., habit formation). A long-standing question in the field is how limbic and sensorimotor domains communicate with each other, and specifically if they do so during the automation of action sequences. It has been suggested that such coordination is implemented by reciprocal loop connections between striatal projection neurons and the dopaminergic midbrain. Although very influential in theory the effectiveness of this limbic-sensorimotor “bridging” principle has yet to be verified. I hypothesize that during the automation of behaviour regional dopamine signalling is governed by a striatal hierarchy and that dysregulation of this coordination leads to compulsive execution of automatic actions characteristic of several psychiatric disorders. To test this hypothesis, we will conduct electrochemical measurements with real-time resolution simultaneously in limbic and sensorimotor striatum to assess the regional coordination of dopamine release in behaving animals. We developed novel chronically implantable electrodes to enable monitoring of dopamine dynamics throughout the development of habitual behaviour and its compulsive execution in transgenic rats - a species suitable for our complex behavioural assays. Novel rabies virus-mediated gene delivery for in vivo optogenetics in these rats will give us the unique opportunity to test whether specific loop pathways govern striatal dopamine transmission and are causally involved in habit formation and compulsive behaviour.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym COREFEAR
Project Functional wiring of the core neural network of innate fear
Researcher (PI) Cornelius Gross
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Call Details Advanced Grant (AdG), LS5, ERC-2013-ADG
Summary Fear is an emotion that exerts powerful effects on our behavior and physiology. A large body of research implicates the amygdala in fear of painful stimuli, but virtually nothing is known about the circuits that support fear of predators and social threats, despite their primal importance in human behavior and pathology. Unlike painful stimuli, predator and social threats activate the medial hypothalamus, a cluster of highly conserved brain nuclei that control motivated behavior. Intriguingly, predator and social threats recruit largely non-overlapping nuclei in the medial hypothalamus, and we have recently demonstrated that separate medial hypothalamic circuits are essential for predator and social fear. We aim to build a functional wiring diagram of predator and social fear in the mouse that will explain how these fears are triggered, coordinated, and remembered. Such a functional wiring diagram will reveal the network logic of innate fear and put us in a position to selectively intervene in fear processing. Electrical stimulation of the medial hypothalamus in humans elicits panic responses and pharmacological agents that block these circuits will offer unexplored therapeutic approaches to treat anxiety disorders such as panic, social phobia, and post-traumatic stress disorder. Moreover, the relatively simple architecture of the medial hypothalamic fear network and its robust and direct behavioral readout in the mouse will be a powerful platform to test the role of several fundamental circuit features that are common to a wide range of behavioral networks, but whose function remains unknown, including the role of feedback loops, sparse cellular encoding of behavior, and overlapping processing of distinct behavioral responses. In this way, the project will provide the first circuit-level understanding of predator and social fear and answer a series of fundamental questions about how neural networks control behavior.
Summary
Fear is an emotion that exerts powerful effects on our behavior and physiology. A large body of research implicates the amygdala in fear of painful stimuli, but virtually nothing is known about the circuits that support fear of predators and social threats, despite their primal importance in human behavior and pathology. Unlike painful stimuli, predator and social threats activate the medial hypothalamus, a cluster of highly conserved brain nuclei that control motivated behavior. Intriguingly, predator and social threats recruit largely non-overlapping nuclei in the medial hypothalamus, and we have recently demonstrated that separate medial hypothalamic circuits are essential for predator and social fear. We aim to build a functional wiring diagram of predator and social fear in the mouse that will explain how these fears are triggered, coordinated, and remembered. Such a functional wiring diagram will reveal the network logic of innate fear and put us in a position to selectively intervene in fear processing. Electrical stimulation of the medial hypothalamus in humans elicits panic responses and pharmacological agents that block these circuits will offer unexplored therapeutic approaches to treat anxiety disorders such as panic, social phobia, and post-traumatic stress disorder. Moreover, the relatively simple architecture of the medial hypothalamic fear network and its robust and direct behavioral readout in the mouse will be a powerful platform to test the role of several fundamental circuit features that are common to a wide range of behavioral networks, but whose function remains unknown, including the role of feedback loops, sparse cellular encoding of behavior, and overlapping processing of distinct behavioral responses. In this way, the project will provide the first circuit-level understanding of predator and social fear and answer a series of fundamental questions about how neural networks control behavior.
Max ERC Funding
2 493 839 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym CorPain
Project Dissection of a cortical microcircuit for the processing of pain affect
Researcher (PI) Thomas Nevian
Host Institution (HI) UNIVERSITAET BERN
Call Details Consolidator Grant (CoG), LS5, ERC-2015-CoG
Summary It is a fundamental but still elusive question how nociceptive processing is performed in neuronal networks in the cortex for the conscious experience of pain.
The objective of this project is to identify and characterize the cortical microcircuits in the anterior cingulate cortex (ACC) that are involved in pain processing with cellular resolution. The ACC is essential for evaluating the emotional/affective component of pain. Our research will investigate the elusive question if a dedicated pain circuit exists in the ACC. We will dissect the detailed structure and connectivity of this pain circuit and investigate how it generates affective behavioural responses related to pain.
At the core of this project, we will characterize the neuronal networks in the ACC that are engaged in the processing of noxious stimuli. It will be highly interesting to determine the neuronal dynamics in the ACC during nociception and in chronic pain conditions on the cellular and network level. Furthermore, we will elucidate the downstream targets that are influenced by the pain circuits in the ACC to generate the appropriate behavioural responses.
These aims will be achieved by a combination of electrophysiology, 2-photon Ca2+ imaging and pharmaco- and opto-genetic approaches both in vivo and in vitro and behavioural testing of pain affect in mice.
This project will give a comprehensive picture of how a cortical microcircuit processes afferent noxious stimuli to generate an affective behavioural response. This study will give important insight into the fundamental question of cortical information processing and it is highly relevant to understand pain processing and the changes in the network dynamics that manifest the transition to chronic pain. Eventually this might contribute to the development of novel treatment strategies for this pathological condition.
Summary
It is a fundamental but still elusive question how nociceptive processing is performed in neuronal networks in the cortex for the conscious experience of pain.
The objective of this project is to identify and characterize the cortical microcircuits in the anterior cingulate cortex (ACC) that are involved in pain processing with cellular resolution. The ACC is essential for evaluating the emotional/affective component of pain. Our research will investigate the elusive question if a dedicated pain circuit exists in the ACC. We will dissect the detailed structure and connectivity of this pain circuit and investigate how it generates affective behavioural responses related to pain.
At the core of this project, we will characterize the neuronal networks in the ACC that are engaged in the processing of noxious stimuli. It will be highly interesting to determine the neuronal dynamics in the ACC during nociception and in chronic pain conditions on the cellular and network level. Furthermore, we will elucidate the downstream targets that are influenced by the pain circuits in the ACC to generate the appropriate behavioural responses.
These aims will be achieved by a combination of electrophysiology, 2-photon Ca2+ imaging and pharmaco- and opto-genetic approaches both in vivo and in vitro and behavioural testing of pain affect in mice.
This project will give a comprehensive picture of how a cortical microcircuit processes afferent noxious stimuli to generate an affective behavioural response. This study will give important insight into the fundamental question of cortical information processing and it is highly relevant to understand pain processing and the changes in the network dynamics that manifest the transition to chronic pain. Eventually this might contribute to the development of novel treatment strategies for this pathological condition.
Max ERC Funding
1 928 125 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym CORTEX
Project Computations by Neurons and Populations in Visual Cortex
Researcher (PI) Matteo Carandini
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Advanced Grant (AdG), LS5, ERC-2008-AdG
Summary Neurons in primary visual cortex (area V1) receive feedforward inputs from thalamic afferents and lateral inputs from other cortical neurons. Little is known about how these components interact to determine the responses of a V1 neuron. One camp ascribes most responses to feedforward mechanisms. The other camp ascribes them mostly to lateral interactions. We propose that these two apparently opposed views can be simply reconciled in a single framework. We hypothesize that area V1 can operate both in a feedforward regime and in a lateral interaction regime, depending on the nature of the stimulus and on the cognitive task at hand, and that the transition from one regime to the other is governed by synaptic inhibition. We will test these hypotheses by recording from individual V1 neurons while monitoring the activity of nearby populations of cortical neurons via multiprobe electrodes. In Aim 1 we will relate the activity of V1 neurons to that of nearby populations. We will use simple measures of correlation and nonlinear models that predict individual spikes to measure how responses depend on a feedforward contribution (the receptive field ) and on a lateral contribution (the connection field ). We will test our first hypothesis, concerning the role of the stimulus in changing this dependence. In Aim 2 we will extend these results to a behaving animal. We will record from V1 of mice performing a 2-alternative forced-choice psychophysical task, and we will test our second hypothesis, concerning the role of the cognitive task in determining the operating regime of the cortex. In Aim 3 we will seek a biophysical interpretation of the functional mechanisms and effective connectivity revealed by the previous Aims. We will test our third hypothesis, concerning the role of synaptic inhibition. The tools involved will include intracellular recordings and optical stimulation in transgenic mice whose cortical neurons are sensitive to light.
Summary
Neurons in primary visual cortex (area V1) receive feedforward inputs from thalamic afferents and lateral inputs from other cortical neurons. Little is known about how these components interact to determine the responses of a V1 neuron. One camp ascribes most responses to feedforward mechanisms. The other camp ascribes them mostly to lateral interactions. We propose that these two apparently opposed views can be simply reconciled in a single framework. We hypothesize that area V1 can operate both in a feedforward regime and in a lateral interaction regime, depending on the nature of the stimulus and on the cognitive task at hand, and that the transition from one regime to the other is governed by synaptic inhibition. We will test these hypotheses by recording from individual V1 neurons while monitoring the activity of nearby populations of cortical neurons via multiprobe electrodes. In Aim 1 we will relate the activity of V1 neurons to that of nearby populations. We will use simple measures of correlation and nonlinear models that predict individual spikes to measure how responses depend on a feedforward contribution (the receptive field ) and on a lateral contribution (the connection field ). We will test our first hypothesis, concerning the role of the stimulus in changing this dependence. In Aim 2 we will extend these results to a behaving animal. We will record from V1 of mice performing a 2-alternative forced-choice psychophysical task, and we will test our second hypothesis, concerning the role of the cognitive task in determining the operating regime of the cortex. In Aim 3 we will seek a biophysical interpretation of the functional mechanisms and effective connectivity revealed by the previous Aims. We will test our third hypothesis, concerning the role of synaptic inhibition. The tools involved will include intracellular recordings and optical stimulation in transgenic mice whose cortical neurons are sensitive to light.
Max ERC Funding
2 499 921 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
Project acronym CORTEX SIMPLEX
Project Function and computation in three-layer cortex
Researcher (PI) Gilles Jean Laurent
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), LS5, ERC-2012-ADG_20120314
Summary "Understanding brain function is one of the outstanding challenges of modern biology. Many studies focus on mammalian neocortex, a modular and versatile structure that operates equally well with different sensory inputs and for perception, planning as well as action. Neocortex, however, is remarkably complex. It contains many cell types, six layers, networks with local and long-range connections, and its study is technically challenging. We propose here to address central issues of cortical computation using a simpler experimental system. Neocortex evolved from a more primitive cortex, likely present in the ancestors of all amniotes. Extant reptiles are closest to this putative ancestor: their cortex contains only three layers, two of which are nearly exclusively neuropilar. Reptilian cortex is also closest to mammals’ old cortices (piriform and hippocampus). Like in mammals, reptilian cortex is modular. Its design, however, is considerably simpler and more ubiquitous than in mammals. Indeed, so far as we know, reptilian primary olfactory and visual cortices are very similar to one another. Finally, certain reptiles such as turtles have evolved biochemical and metabolic adaptations to resist long periods of anoxia. Thus, their brains can be studied ex vivo over long periods, giving experimenters access to the entire brain with an intact retina or nasal epithelium. We will use this system to study cortical computation, primarily in visual and olfactory areas. Using electrophysiological, imaging, molecular, behavioral and computational methods, we will discover the representational strategies of these two cortices in vivo, the functional architecture of their microcircuits and the computations that they carry out. This understanding of generic and ancient units of cortical computation will illuminate our studies of more complex and sophisticated cortical circuits."
Summary
"Understanding brain function is one of the outstanding challenges of modern biology. Many studies focus on mammalian neocortex, a modular and versatile structure that operates equally well with different sensory inputs and for perception, planning as well as action. Neocortex, however, is remarkably complex. It contains many cell types, six layers, networks with local and long-range connections, and its study is technically challenging. We propose here to address central issues of cortical computation using a simpler experimental system. Neocortex evolved from a more primitive cortex, likely present in the ancestors of all amniotes. Extant reptiles are closest to this putative ancestor: their cortex contains only three layers, two of which are nearly exclusively neuropilar. Reptilian cortex is also closest to mammals’ old cortices (piriform and hippocampus). Like in mammals, reptilian cortex is modular. Its design, however, is considerably simpler and more ubiquitous than in mammals. Indeed, so far as we know, reptilian primary olfactory and visual cortices are very similar to one another. Finally, certain reptiles such as turtles have evolved biochemical and metabolic adaptations to resist long periods of anoxia. Thus, their brains can be studied ex vivo over long periods, giving experimenters access to the entire brain with an intact retina or nasal epithelium. We will use this system to study cortical computation, primarily in visual and olfactory areas. Using electrophysiological, imaging, molecular, behavioral and computational methods, we will discover the representational strategies of these two cortices in vivo, the functional architecture of their microcircuits and the computations that they carry out. This understanding of generic and ancient units of cortical computation will illuminate our studies of more complex and sophisticated cortical circuits."
Max ERC Funding
2 496 111 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
