Skip to main content

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

Objective

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.

Field of science

  • /engineering and technology/electrical engineering, electronic engineering, information engineering/electronic engineering/signal processing
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes
  • /natural sciences/biological sciences/biochemistry/biomolecules/lipids

Call for proposal

ERC-2009-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

KIRSERLETI ORVOSTUDOMANYI KUTATOINTEZET
Address
Szigony Utca 43
1083 Budapest
Hungary
Activity type
Research Organisations
EU contribution
€ 1 638 000
Principal investigator
István Katona (Dr.)
Administrative Contact
Norbert Rozs (Mr.)

Beneficiaries (1)

KIRSERLETI ORVOSTUDOMANYI KUTATOINTEZET
Hungary
EU contribution
€ 1 638 000
Address
Szigony Utca 43
1083 Budapest
Activity type
Research Organisations
Principal investigator
István Katona (Dr.)
Administrative Contact
Norbert Rozs (Mr.)