Project

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Platform for integrated mouse behavior (PIMB)

Applicant Lüscher Christian
Number 139229
Funding scheme R'EQUIP
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.12.2011 - 31.05.2013
Approved amount 408'275.00
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Lay Summary (English)

Lead
Lay summary
This is a platform that aims as establishing several test for mouse behavior. A special emphasis will be given to the dynamic control of the mouse behavior using optiogenetic (i.e. selective activation of brain cells with blue light). approaches.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Publications

Publication
A comparison of striatal-dependant behaviors in wild-type and hemizygous Drd1a and Drd2 BAC transgenic mice
Nelson AB Hang GB Grueter BA Pascoli V Lüscher C Malenka RC Kreitzer AC. (2012), A comparison of striatal-dependant behaviors in wild-type and hemizygous Drd1a and Drd2 BAC transgenic mice, in J Neurosci, 9119-23.
Dense representation of natural odorants in the mouse olfactory bulb
Vincis R. Gschwend O. Bhaukaurally K. Beroud J. and Carleton A. (2012), Dense representation of natural odorants in the mouse olfactory bulb, in Nature Neuroscience , 537-39.
Encoding odorant identity by spiking packets of rate-invariant neurons in awake mice
Gschwend O. Beroud J. and Carleton A. (2012), Encoding odorant identity by spiking packets of rate-invariant neurons in awake mice, in Plos One, 1-12.
GABA neurons of the VTA drive conditioned place aversion
Tan KR Yvon C Turiault M Mirzabekov JJ Doehner J Labouèbe G Deisseroth K Tye KM & Lüscher C. (2012), GABA neurons of the VTA drive conditioned place aversion, in Neuron, 1173-83.
Similar odor discrimination behavior in head-restrained and freely moving mice.
Abraham N. Guerin D. Bhaukaurally K. and Carleton A. (2012), Similar odor discrimination behavior in head-restrained and freely moving mice., in Plos One, 1-10.
Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning
Brown MTC Tan KR O’Connor EC Nikonenko I Muller D & Lüscher C. (2012), Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning, in Nature, 452-6.
Odor representations in the olfactory bulb evolve after the first breath and persist as an odor afterimage.
Patterson M.A. Lagier S. and Carleton A., Odor representations in the olfactory bulb evolve after the first breath and persist as an odor afterimage., in Proc. Nat. Acad. Sci.

Scientific events



Self-organised

Title Date Place
Synaptic Basis of Disease 10.07.2012 Geneva, Switzerland

Associated projects

Number Title Start Funding scheme
135631 Long-term potentiation and the modification of synaptic structures in vivo 01.04.2011 Project funding (Div. I-III)
154453 Function and structure of neuromodulatory inputs to the cerebral cortex 01.01.2015 Sinergia
132729 Spiraling towards relapse: a network approach to addiction 01.10.2010 Project funding (Div. I-III)
119169 Maturation of adult-born interneurons and consequences on sensory perception 01.04.2008 SNSF Professorships
127289 Structure, Function and Plasticity of the Barrel Cortex 01.01.2010 Sinergia
125115 NOX enzymes and redox regulation in the central nervous system: studies using genetically modified rodents and pluripotent stem cells 01.04.2009 Project funding (Div. I-III)
120685 Experience-dependent structural plasticity of synapses in vivo 01.04.2008 Project funding (Div. I-III)

Abstract

1. SummaryBackground - In order to produce an accurate model of how the brain controls behavior we need to study the brain’s activity in relation to behavior from two perspectives. First, we need to monitor the activity of ensembles of neurons with single cell and high temporal resolution during the behavior. Second, we need to manipulate particular neuronal populations and assess the effects on the behavior. Despite a rapid progress in functional imaging in humans, truly mechanistic investigations of neuronal network function in relation to behavior can currently only be performed efficiently in animal models. We therefore propose to establish a platform for integrated mouse behavior (PIMB). The strength of this platform resides in its integrated design: combining the observation of mouse behavior with electrophysiological and optical recordings as well as optogenetic control of neuronal activity. The PIMB will benefit from broad expertise that is present in its supporting laboratories, ranging from genetic manipulation, electrophysiology, and imaging in vivo, to retrospective characterization of neurons in brain slices by electrophysiology, histology and electron microscopy. With help of the faculty of medicine, part of the platform is currently being installed in the CMU in Geneva. It is in close proximity to the applicants’ labs, warranting optimal accessibility and minimal transport-related stress to mice.Research proposal - The present proposal is a revised version of a project that was submitted last year. It is supported by four core applicants, each with a specific project. Notwithstanding, the PIMB will be open to any group in the medical faculty who has an interest in investigating mouse behavior. Each of the four members is currently carrying out experiments using mouse behavior, several of which have been published (see offprints attached). Since the original submission we have been able to secure support from the faculty of medicine, such that all of the core infrastructure has been taken care of (i.e. half of the total budget: special requirements for mouse-housing, ventilated cages, basic setups with video tracking systems, Skinner boxes, etc). We are still lacking essential elements to make this platform truly integrative, such as multisite electrophysiological recording devices and devices for precise optical control of neuronal activity (i.e. optrodes, electrodes with integrated fiber optics). The platform will comprise one operating room for stereotaxic injections/lesions and three behavior rooms. Each room is subdivided into a separate mouse-housing compartment for acclimatization and an experimental part (Figure 1). The platform will be managed by a part-time technician. Its operating budget will rely on institutional funds, fixed contributions from the core users, and hourly fees charged to other users. The core users will use the PIMB to investigate the role of: 1) activity and plasticity of the midbrain dopamine system in addictive behavior (Lüscher, principal applicant); 2) network processing in the olfactory system in odor discrimination (Carleton); 3) cortical structural plasticity in sensory learning (Holtmaat); and 4) NOX signaling in learning (Krause). Basic setups, such as mazes, rotarods, hot plates, open fields, “intellicages”, light/dark cages, and fear conditioning boxes will also allow analysis of spatial learning (Muller), sensory and motor function (Jabaudon), regeneration and analgesia (Kiss), explorative and social behavior (Vutskits, Hüppi), anxiety behavior (Dayer), and place preference (Muhlethaler).Expected value - The PIMB will allow the parallel analysis of behavior and neuronal network function. Correlating neuronal activity with behavior and vice versa is essential to obtain a deeper understanding of how the brain instructs behavior. Such studies also present an important step towards translational research, aiming at elucidating the neuronal basis of mental diseases, such as addiction, depression and schizophrenia, as well as for strategies to combat neurodegenerative disorders, such as Alzheimer’s.Justification of equipment needed - There is a pressing demand for a behavioral testing platform in close proximity to the neuroscience laboratories in the CMU. The faculty has partly met this demand by providing rooms and some basic equipment, but the incorporation of electrophysiology equipment and the optogenetic control is essential, and still lacking. An integrated platform at this scale will to the best of our knowledge be unique in Switzerland. The PIMB will directly benefit a large number of researchers within the faculty of medicine, but will also be accessible to researchers outside of Geneva who are interested in integrative behavioral testing.
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