Impact of Afferent Inputs on Purkinje Cell Spiking Patterns and Motor Coordination

The brain is what makes us human. Feelings, memories, complex social interactions, language and movement – all of it originates in the brain. On average, the human brain contains approximately 50–100 billion neurons that communicate with each other through the vast network of 100 – 500 trillion connections called synapses. More than half of the total number of neurons make a structure called the cerebellum. In vertebrates, the cerebellum (Latin for little brain) controls movement and monitors its efficiency by collecting sensory information such as visual cues, limb positions and balance. This information is necessary to adequately respond to the environment by controlling and correcting the movements. Historically, since the 18th century when Arne – Charles Lorry showed that the damage to this structure results in loss of motor coordination1, the cerebellum has been known to be involved in motor coordination. In the 19th century neurophysiologists such as Luigi Rolando and Jean Pierre Flourens revealed that animals with cerebellar damage can still move, but with a loss of coordination and that recovery after the lesion can be nearly complete unless the lesion is very extensive2. The milestone for understanding the cerebellum was placed by the research of Camillo Golgi and Satiago Ramon y Cajal in the late 1800s. The work of these anatomists enabled visualization of individual neurons revealing for the first time the structural organization of the brain, including the cerebellum. More than a century later researchers still battle with two main questions. Firstly, how does the cerebellar function contribute and/or results in such a sophisticated level of motor coordination that enables us to do things like playing the violin or ballroom dancing? Secondly, how do we acquire those new motor skills? The cerebellar network seems to be holding the key to answering both of those questions. It has the capacity to process the sensory information and translate it into a motor command. In this thesis, we describe the effects of alteration in the cerebellar system unraveling the possible role of its afferent inputs

Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments

Translating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model o

Glissades Are Altered by Lesions to the Oculomotor Vermis but Not by Saccadic Adaptation

Saccadic eye movements enable fast and precise scanning of the visual field, which is partially controlled by the posterior cerebellar vermis. Textbook saccades have a straight trajectory and a unimodal velocity profile, and hence have well-defined epochs of start and end. However, in practice only a fraction of saccades matches this description. One way in which a saccade can deviate from its trajectory is the presence of an overshoot or undershoot at the end of a saccadic eye movement just before fixation. This additional movement, known as a glissade, is regarded as a motor command error and was characterized decades ago but was almost never studied. Using rhesus macaques, we investigated the properties of glissades and changes to glissade kinematics following cerebellar lesions. Additionally, in monkeys with an intact cerebellum, we investigated whether the glissade amplitude can be modulated using multiple adaptation paradigms. Our results show that saccade kinematics are altered by the presence of a glissade, and that glissades do not appear to have any adaptive function as they do not bring the eye closer to the target. Quantification of these results establishes a detailed description of glissades. Further, we show that lesions to the posterior cerebellum have a deleterious effect on both saccade and glissade properties, which recovers over time. Finally, the saccadic adaptation experiments reveal that glissades cannot be modulated by this training paradigm. Together our work offers a functional study of glissades and provides new insight into the cerebellar involvement in this type of motor error