Project acronym BRAINCANNABINOIDS
Project Understanding the molecular blueprint and functional complexity of the endocannabinoid metabolome in the brain
Researcher (PI) István Katona
Host Institution (HI) INSTITUTE OF EXPERIMENTAL MEDICINE - HUNGARIAN ACADEMY OF SCIENCES
Call Details Starting Grant (StG), LS5, ERC-2009-StG
Summary We and others have recently delineated the molecular architecture of a new feedback pathway in brain synapses, which operates as a synaptic circuit breaker. This pathway is supposed to use a group of lipid messengers as retrograde synaptic signals, the so-called endocannabinoids. Although heterogeneous in their chemical structures, these molecules along with the psychoactive compound in cannabis are thought to target the same effector in the brain, the CB1 receptor. However, the molecular catalog of these bioactive lipids and their metabolic enzymes has been expanding rapidly by recent advances in lipidomics and proteomics raising the possibility that these lipids may also serve novel, yet unidentified physiological functions. Thus, the overall aim of our research program is to define the molecular and anatomical organization of these endocannabinoid-mediated pathways and to determine their functional significance. In the present proposal, we will focus on understanding how these novel pathways regulate synaptic and extrasynaptic signaling in hippocampal neurons. Using combination of lipidomic, genetic and high-resolution anatomical approaches, we will identify distinct chemical species of endocannabinoids and will show how their metabolic enzymes are segregated into different subcellular compartments in cell type- and synapse-specific manner. Subsequently, we will use genetically encoded gain-of-function, loss-of-function and reporter constructs in imaging experiments and electrophysiological recordings to gain insights into the diverse tasks that these new pathways serve in synaptic transmission and extrasynaptic signal processing. Our proposed experiments will reveal fundamental principles of intercellular and intracellular endocannabinoid signaling in the brain.
Summary
We and others have recently delineated the molecular architecture of a new feedback pathway in brain synapses, which operates as a synaptic circuit breaker. This pathway is supposed to use a group of lipid messengers as retrograde synaptic signals, the so-called endocannabinoids. Although heterogeneous in their chemical structures, these molecules along with the psychoactive compound in cannabis are thought to target the same effector in the brain, the CB1 receptor. However, the molecular catalog of these bioactive lipids and their metabolic enzymes has been expanding rapidly by recent advances in lipidomics and proteomics raising the possibility that these lipids may also serve novel, yet unidentified physiological functions. Thus, the overall aim of our research program is to define the molecular and anatomical organization of these endocannabinoid-mediated pathways and to determine their functional significance. In the present proposal, we will focus on understanding how these novel pathways regulate synaptic and extrasynaptic signaling in hippocampal neurons. Using combination of lipidomic, genetic and high-resolution anatomical approaches, we will identify distinct chemical species of endocannabinoids and will show how their metabolic enzymes are segregated into different subcellular compartments in cell type- and synapse-specific manner. Subsequently, we will use genetically encoded gain-of-function, loss-of-function and reporter constructs in imaging experiments and electrophysiological recordings to gain insights into the diverse tasks that these new pathways serve in synaptic transmission and extrasynaptic signal processing. Our proposed experiments will reveal fundamental principles of intercellular and intracellular endocannabinoid signaling in the brain.
Max ERC Funding
1 638 000 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym OSTREFCOM
Project Human infants' preparedness for relevance-guided learning through ostensive-referential communication
Researcher (PI) Gergely Csibra
Host Institution (HI) KOZEP-EUROPAI EGYETEM
Call Details Advanced Grant (AdG), SH4, ERC-2009-AdG
Summary A recent hypothesis (the theory of 'natural pedagogy') proposes that an important function of human ostensive-referential communication is to allow the transmission of generic (semantic) knowledge to others. The primary potential beneficiaries of such a communication system are children, who are always novices with respect to the culture they are born into. This proposal aims to explore whether and how human infants are prepared to learn from adults through communication, what cognitive and neural systems support such learning process, and how this social learning process changes infants' perception, interpretation and representation of the world. Beyond traditional behavioural methods, we plan to use eye-tracking, electrophysiological (EEG, ERP) and optical imaging (NIRS) techniques to get insights about the online processes of perception, attention and memory during, as well as the understanding of the social and physical world through, non-verbal communication. In particular, we seek to track (1) the early development of sensitivity to various ostensive-communicative signals, (2) their relation to the understanding of referential deictic gestures, which is essential to be engaged in triadic communication, (3) how these signals modulate what infants pay attention to and preserve in their memory about objects, and (4) how the functional understanding of human-made cultural artefacts (such as tools) is affected by their demonstrated use in ostensive-referential communicative settings. The new framework theory of natural pedagogy will also provide a novel perspective to elucidate how further cognitive systems, such as the understanding of actions or causal relations, as well as the processes of imitation and word learning contribute to cultural learning by communication.
Summary
A recent hypothesis (the theory of 'natural pedagogy') proposes that an important function of human ostensive-referential communication is to allow the transmission of generic (semantic) knowledge to others. The primary potential beneficiaries of such a communication system are children, who are always novices with respect to the culture they are born into. This proposal aims to explore whether and how human infants are prepared to learn from adults through communication, what cognitive and neural systems support such learning process, and how this social learning process changes infants' perception, interpretation and representation of the world. Beyond traditional behavioural methods, we plan to use eye-tracking, electrophysiological (EEG, ERP) and optical imaging (NIRS) techniques to get insights about the online processes of perception, attention and memory during, as well as the understanding of the social and physical world through, non-verbal communication. In particular, we seek to track (1) the early development of sensitivity to various ostensive-communicative signals, (2) their relation to the understanding of referential deictic gestures, which is essential to be engaged in triadic communication, (3) how these signals modulate what infants pay attention to and preserve in their memory about objects, and (4) how the functional understanding of human-made cultural artefacts (such as tools) is affected by their demonstrated use in ostensive-referential communicative settings. The new framework theory of natural pedagogy will also provide a novel perspective to elucidate how further cognitive systems, such as the understanding of actions or causal relations, as well as the processes of imitation and word learning contribute to cultural learning by communication.
Max ERC Funding
1 557 428 €
Duration
Start date: 2010-05-01, End date: 2015-10-31
