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dc.contributor.authorMasullo, Laura
dc.date.accessioned2020-01-09T16:47:51Z
dc.date.available2020-01-09T16:47:51Z
dc.date.issued2020-05-16
dc.date.submitted2019-04-01
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/300662
dc.description.abstractIn order to successfully interact with the environment, animals need to produce accurate movements towards specific positions in space. A crucial region of the brain that guides such goal-oriented movements is the superior colliculus (SC), an evolutionary conserved structure of the midbrain. While several lines of research in different model organisms have confirmed that the SC contributes to the initiation of orienting movements, how functionally distinct neuronal groups within the SC are organized to support the production of such motor outputs is poorly understood. One of the reasons why the intrinsic circuit organization of the SC remains elusive is the lack of genetic characterization of the neuronal populations of the motor SC. Here, we performed RNAseq to screen for genetic markers for neuronal subpopulations in the motor SC. We identified a transcription factor, Pitx2, which is exclusively expressed in a subpopulation of glutamatergic neurons in the motor domain of the SC. Strikingly, this population of neurons displays a non-homogenous distribution within the motor layer of the SC, being organised in clusters along the mediolateral and anteroposterior axis. We mapped the pre-synaptic network and the post-synaptic targets of Pitx2ON neurons, unveiling that this modular population receives direct inputs from motor and sensory cortical regions, as well as several midbrain nuclei involved in movement control, and sends projection along the cephalomotor pathway. We then asked whether these modules may act as functional units, each integrating multimodal sensory information and encoding a specific feature of head movement, the main ethologically relevant orienting behaviour in rodents. Optogenetic activation of this modular population in freely moving animals produced a stereotyped, robust head motion characterised by a pronounced quantal nature; furthermore, the amplitude of the elicited head movement varied based on the modular unit activated. Our results suggest that distinct clusters of genetically defined neurons produce head displacement along a characteristic vector. In conclusion, we found that a population of premotor neurons in the SC is organised in a modular conformation and we suggest that such modularity may represent a physical implementation of a discontinuous motor map for orienting movements encoded in the mouse SC. Our work complements previous observations of periodicity in SC circuitry, as well as its afferent and efferent systems. Exploiting the genetic toolkit available in the mouse, our work begins to address the functional relevance of this modularity and paves the way for future experiments to investigate principles of sensorimotor integration in SC circuits.
dc.description.sponsorshipMRC
dc.language.isoen
dc.rightsAll rights reserved
dc.rightsAll Rights Reserveden
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/en
dc.subjectsuperior colliculus
dc.subjectPitx2
dc.subjectmotor control
dc.subjecthead movement
dc.subjectorienting behaviour
dc.subjectneurogenetics
dc.subjectRNAseq
dc.subjectviral tracing
dc.subjectoptogenetics
dc.titleGenetic dissection of circuits underlying the modular structure of the Superior Colliculus
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.publisher.departmentMRC Laboratory of Molecular Biology
dc.date.updated2020-01-09T16:35:20Z
dc.identifier.doi10.17863/CAM.47735
dc.publisher.collegePeterhouse
dc.type.qualificationtitlePhD in Biological Sciences
cam.supervisorTripodi, Marco
cam.thesis.fundingtrue


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