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Optogenetic Analysis of Serotonin Function in the Mammalian Brain

Objective

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.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/computer and information sciences/data science/data processing

Call for proposal

ERC-2009-AdG
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Address
Avenida Brasilia, Centro De Investigacao Da Fundacao Champalimaud
1400-038 Lisboa
Portugal
Activity type
Research Organisations
EU contribution
€ 1 401 513,99
Principal investigator
Zachary Mainen (Dr.)
Administrative Contact
Tania Vinagre (Dr.)

Beneficiaries (2)

FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Portugal
EU contribution
€ 1 401 513,99
Address
Avenida Brasilia, Centro De Investigacao Da Fundacao Champalimaud
1400-038 Lisboa
Activity type
Research Organisations
Principal investigator
Zachary Mainen (Dr.)
Administrative Contact
Tania Vinagre (Dr.)
FUNDACAO CALOUSTE GULBENKIAN

Participation ended

Portugal
EU contribution
€ 917 122,41
Address
Avenida Berna 45
1000 Lisboa
Activity type
Research Organisations
Administrative Contact
José Mario Leite (Mr.)