Relatório Anual 2010 - Fundação Champalimaud

RESEARCH GROUPSMegan R. CareyNeural Circuits and BehaviorWe are interested in the neural basis of behavior – how activity in neuralcircuits enables us to interact appropriately with the world around us. Ourresearch focuses on the cerebellum, a brain area that plays a central rolein coordinated motor control and motor learning. Our goal is to understandhow cellular processes within the cerebellum contribute to specific aspectsof behavior. We use transgenic mice to specifically perturb cellular processesin identified neuronal populations and dissect cerebellar circuit function.Endocannabinoids in cerebellar learningCannabinoids are powerful neuromodulators that are responsible for thepsychotropic effects of marijuana and mediate several forms of synapticplasticity. In the cerebellum, both short- and long-term plasticity betweenparallel fibers and Purkinje cells depend on activation of cannabinoidreceptors (CB1Rs). Recently we have shown, using cell type-specific CB1knockout mice, that CB1Rs on cerebellar parallel fibers are required forthis plasticity. We are now using these mice to examine the behavioralconsequences of CB1R deletion from parallel fibers. Specifically, we aretesting the hypothesis that CB1-dependent long-term depression is requiredfor a simple form of learning, classical eyelid conditioning.Cerebellar circuit diagram.The known anatomy and connectivityof the cerebellar circuit allows us toperturb cellular and synaptic functionsof identified cell typesand assess the effects on behavior.Cellular and circuit analysis of genetic perturbationsWe take advantage of the molecular identifiability and known connectivitiesof cerebellar neurons to make targeted perturbations of the cerebellar circuit.Existing technologies allow us to knock out or selectively express individualmolecules in identified cell types. We will use in vitro electrophysiology andcalcium imaging to characterize the effects of these manipulations on neuralexcitability, synaptic transmission, and plasticity. Our goal is to acquirea detailed understanding of the contribution of individual molecular andcellular elements to overall circuit function.Development of new behavioral assaysThe cerebellum performs complex feats of motor coordination. Yet, behavioralassessments of cerebellar circuit function in mice are typically limited eitherto general measures of coordination or relatively simple forms of associativelearning. We are working to establish new, quantitative measures of cerebellarfunction. By comparing specific aspects of behavior across mice in which geneticperturbations have been targeted to different individual neuronal types,we hope to determine links between cellular and circuit function and behavior.FC Relatório Anual 2010 18