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Understanding the molecular blueprint and functional complexity of the endocannabinoid metabolome in the brain

Objetivo

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.

Convocatoria de propuestas

ERC-2009-StG
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Régimen de financiación

ERC-SG - ERC Starting Grant

Institución de acogida

HUN REN KISERLETI ORVOSTUDOMANYI KUTATOINTEZET
Aportación de la UE
€ 1 638 000,00
Dirección
SZIGONY UTCA 43
1083 Budapest
Hungría

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Región
Közép-Magyarország Budapest Budapest
Tipo de actividad
Research Organisations
Contacto administrativo
Norbert Rozs (Mr.)
Investigador principal
István Katona (Dr.)
Enlaces
Coste total
Sin datos

Beneficiarios (1)