Project acronym 5HT-OPTOGENETICS
Project Optogenetic Analysis of Serotonin Function in the Mammalian Brain
Researcher (PI) Zachary Mainen
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary 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.
Summary
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.
Max ERC Funding
2 318 636 €
Duration
Start date: 2010-07-01, End date: 2015-12-31
Project acronym EXOEARTHS
Project EXtra-solar planets and stellar astrophysics: towards the detection of Other Earths
Researcher (PI) Nuno Miguel Cardoso Santos
Host Institution (HI) CENTRO DE INVESTIGACAO EM ASTRONOMIA E ASTROFISICA DA UNIVERSIDADE DO PORTO
Call Details Starting Grant (StG), PE9, ERC-2009-StG
Summary The detection of more than 300 extrasolar planets orbiting other solar-like stars opened the window to a new field of astrophysics. Many projects to search for Earth-like planets are currently under way, using a huge battery of telescopes and instruments. New instrumentation is also being developed towards this goal for use in both ground- and space-based based facilities. Since planets come as an output of the star formation process, the study of the stars hosting planets is of great importance. The stellar-planet connection is strengthened by the fact that most of the exoplanets were discovered using a Doppler radial-velocity technique, where the gravitational influence of the planet on the star and not the planet itself is actually measured. This project aims at doing frontier research to explore i) in unique detail the stellar limitations of the radial-velocity technique, as well as ways of reducing them, having in mind the detection of Earth-like planets and ii) to develop and apply software packages aiming at the study of the properties of the planet-host stars, having in mind the full characterization of the newfound planets, as well as understanding planet formation processes. These goals will improve our capacity to detect, study, and characterize new very low mass extra-solar planets. EXOEarths further fits into the fact that I am currently Co-PI of the project for a new high-resolution ultra-stable spectrograph for the VLT. The results of this project are crucial to fully exploit this new instrument. They will be also of extreme importance to current state-of-the-art planet-search projects aiming at the discovery of other Earths, in particular those making use of the radial-velocity method.
Summary
The detection of more than 300 extrasolar planets orbiting other solar-like stars opened the window to a new field of astrophysics. Many projects to search for Earth-like planets are currently under way, using a huge battery of telescopes and instruments. New instrumentation is also being developed towards this goal for use in both ground- and space-based based facilities. Since planets come as an output of the star formation process, the study of the stars hosting planets is of great importance. The stellar-planet connection is strengthened by the fact that most of the exoplanets were discovered using a Doppler radial-velocity technique, where the gravitational influence of the planet on the star and not the planet itself is actually measured. This project aims at doing frontier research to explore i) in unique detail the stellar limitations of the radial-velocity technique, as well as ways of reducing them, having in mind the detection of Earth-like planets and ii) to develop and apply software packages aiming at the study of the properties of the planet-host stars, having in mind the full characterization of the newfound planets, as well as understanding planet formation processes. These goals will improve our capacity to detect, study, and characterize new very low mass extra-solar planets. EXOEarths further fits into the fact that I am currently Co-PI of the project for a new high-resolution ultra-stable spectrograph for the VLT. The results of this project are crucial to fully exploit this new instrument. They will be also of extreme importance to current state-of-the-art planet-search projects aiming at the discovery of other Earths, in particular those making use of the radial-velocity method.
Max ERC Funding
928 090 €
Duration
Start date: 2009-10-01, End date: 2014-12-31
Project acronym NEUROHABIT
Project Neural mechanisms of action learning and action selection: from intent to habit
Researcher (PI) Rui Manuel Marques Fernandes Da Costa
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Starting Grant (StG), LS5, ERC-2009-StG
Summary In every day life, we constantly have to select the appropriate actions to obtain specific outcomes. Actions can be selected based on their consequences, for example when we press an elevator button to get to the particular floor where we live. This goal-directed behaviour is crucial to face the ever-changing environment but demands an effortful control and monitoring of the response; one way to balance the need for flexibility and efficiency is through automatization of recurring decision processes as a habit. Habitual responses no longer need the evaluation of their consequences, and can be elicited by particular situations or stimuli, for example when we press the button for our home floor in a building that we are visiting for the first time. There is growing evidence that the neural circuits underlying intentional or goal-directed actions are different from those underlying habits; associative corticostriatal circuits have been implicated in goal-directed actions, and sensorimotor circuits in habit formation. Dopamine (DA) has been implicated in both voluntary actions and habits. However, DA neurons from the VTA and the SNc project to different cortical and striatal regions, and the specific role of VTA and SNc DA in goal-directed actions and habits has not been clarified. We propose to: 1) use cell-type and region specific genetic manipulations to test if phasic firing in VTA or SNc DA neurons is necessary for goal-directed actions or habits, respectively, 2) generate cell-type specific channelrodhopsin transgenic mice to test if phasic DA neuron firing in these areas is sufficient to produce goal-directed actions or habits, and 3) selectively manipulate striatal neurons modulated by VTA or SNc phasic DA to test if they are necessary for goal-directed actions or habits. The dissection of the molecular and circuit mechanisms underlying goal-directed and habitual responses will be critical to understand decision-making, and the origins of compulsive behaviour.
Summary
In every day life, we constantly have to select the appropriate actions to obtain specific outcomes. Actions can be selected based on their consequences, for example when we press an elevator button to get to the particular floor where we live. This goal-directed behaviour is crucial to face the ever-changing environment but demands an effortful control and monitoring of the response; one way to balance the need for flexibility and efficiency is through automatization of recurring decision processes as a habit. Habitual responses no longer need the evaluation of their consequences, and can be elicited by particular situations or stimuli, for example when we press the button for our home floor in a building that we are visiting for the first time. There is growing evidence that the neural circuits underlying intentional or goal-directed actions are different from those underlying habits; associative corticostriatal circuits have been implicated in goal-directed actions, and sensorimotor circuits in habit formation. Dopamine (DA) has been implicated in both voluntary actions and habits. However, DA neurons from the VTA and the SNc project to different cortical and striatal regions, and the specific role of VTA and SNc DA in goal-directed actions and habits has not been clarified. We propose to: 1) use cell-type and region specific genetic manipulations to test if phasic firing in VTA or SNc DA neurons is necessary for goal-directed actions or habits, respectively, 2) generate cell-type specific channelrodhopsin transgenic mice to test if phasic DA neuron firing in these areas is sufficient to produce goal-directed actions or habits, and 3) selectively manipulate striatal neurons modulated by VTA or SNc phasic DA to test if they are necessary for goal-directed actions or habits. The dissection of the molecular and circuit mechanisms underlying goal-directed and habitual responses will be critical to understand decision-making, and the origins of compulsive behaviour.
Max ERC Funding
1 526 304 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
