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EFFECTS OF DEEP BRAIN STIMULATION OF THE DORSAL RAPHE NUCLEUS ON BEHAVIORAL DEFENSIVE RESPONSES RELATED TO ANXIETY AND ON ELECTROPHYSIOLOGICAL RECORDINGS OF NEURONAL SUBPOPULATIONS OF THE VENTRAL HIPPOCAMPUS
One of the main neurochemical systems related to anxiety and panic responses is the serotonergic system, arising from the dorsal raphe nucleus (DR). Previous evidence suggests that the DR is not homogeneous, but a group of distinct neuronal subpopulations, with morphological and functional differences. The dorsal region of the dorsal raphe (DRD) seems to be critically involved with the regulation of anxiety-related responses. In fact, a previous study from our research group showed that Deep Brain Stimulation (DBS) applied to this DR subregion induced anxiolytic-like effects, followed by increases in c-Fos-immunoreactivity (Fos-ir) in prosencephalic regions that receive serotonergic innervation from the DR. Although c-Fos is an important marker of neuronal activity, these results do not allow the understanding of what happened to the serotonergic modulation of the brain regions that showed increased Fos-ir. The purpose of the present study is to better investigate the mechanisms through which DBS induces anxiolytic-like effects. For that, both behavioral and electrophysiological measurements will be performed. The behavioral measurements will allow the verification of the generalization of the anxiolytic-like effects of DBS applied to the DRD. For that another animal model of anxiety will be used, the light-dark transition model. The electrophysiological recordings will be performed in an important brain region associated to the regulation of anxiety and that receives serotonin innervation from the DRD, the ventral hippocampus. A week after the implant of the electrodes, male Wistar rats will be submitted to high frequency stimulation of the DRD (100 µA, 100 Hz) for 1 h. Immediately after, they will be tested in the light-dark transition model. Control animals will not be stimulated, but will remain for the same period of time attached to the stimulator. After the behavioral measurements, the animals will be decapitated and their brains removed. Histological slices of the ventral hippocampus (CA3 region) will be used for the ex vivo electrophysiological recordings. The present study will help to understand the neurophysiological mechanisms of action of DBS. At last, it is important to emphasize that the present study will also allow the learning of the technique of ex vivo eletrophysiological recordings and its incorporation to the research group of the candidate at UNIFESP, campus Baixada Santista.
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