Research Grants 15/09550-9 - Epilepsia, Cerebelo - BV FAPESP
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Physiological characterization of the cerebellum of the neotropical rodent proechimys

Abstract

During his visit, Professor Tycho Hoogland will conduct experiments and teach techniques of electrophysiology in vivo and in vitro and he will participate in a number of institutional activities, such as lectures and formal and informal discussions. Prof. Tycho will teach a postgraduate course organized in two parts: 1) "Optical readout of neural activity (imaging the brain) e 2) Optical control of neural activity (stimulating the brain with light). The central objective of the seminares is to provide attendees with the conceptual tools necessary to perform high-end in vitro and in vivo electrophysiology of the brain, even with limited resources and equipment, tailored to key neuroscientific questions. The course will focus on multidisciplinarity, linking functional morphology, electrophysiology and behavior in both physiological and pathological (epilepsy) contexts. In addition, this collaboration launches a new line of investigation in our laboratory using innovative experimental approaches to explores the activity of cerebellar networks in the Neotropical rodent Proechimys. Proechimys is known as an animal resistant to epilepsy, presenting endogenous antiepileptogenic mechanisms. Several findings suggested that the overall circuit function in these rodents is quite distinct from that in other rodents such as Wistar and Sprague-Dawley rats. Proechimys pups display cage exploration shortly after birth suggesting that the neural circuitry to guide complex movements develops at a very early stage. Because of the role of the cerebellum in coordination and motor control it would be of great interest to study for the first time the physiology and function of the cerebellum in these Amazonian rodents. The goal of this project will therefore be to begin with characterizing the physiology of neurons in the cerebellar cortex of Proechimys by performing in vivo extracellular recordings under light anesthesia. Our aim is to quantify the firing properties of molecular layer interneurons, Purkinje cells and granule cell layer activity. In addition, we will apply short air puffs to the whiskers while recording in Crus I of the cerebellum, an area with strong whisker receptive fields to characterize the responsiveness of Purkinje cells to aversive air puff stimuli, which typically evoke stimulus-locked complex spikes. These will be the first in vivo physiology experiments performed in Proechymis in the world and will establish these in vivo extracellular recordings at UNIFESP. Histology will be performed on cerebellum of Proechimys to characterize the overall morphology of the cerebellum, its foliation and the size of molecular layer interneurons, Purkinje cells and granule cells for comparison with Wistar rats. Future experiments will therefore explore first how cerebellar neurons respond during evoked epileptic seizures and second how optogenetic manipulation of Purkinje cells and/or cerebellar nuclei neurons attenuates seizures in Proechymis (AU)

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