Sepsis, a systemic inflammatory condition triggered by an infectious agent, induces an inflammatory status in central nervous system (CSN) which leads to autonomic, cognitive and behavioral alterations. The paraventricular nucleus of the hypothalamus (PVN) plays a major role in endocrine control during sepsis and is associated to the regulation of neurohypophyseal hormones and HPA axis. One of the main connections to PVN is the central nucleus of the amygdala (CeA), that in septic animals was found to be susceptible to microglial and synaptic alterations. However, it is not known how sepsis alters the communication between these nuclei and leads to endocrine alterations. In order to elucidate this question, we will first use immunostaining and transgenic mice to temporally evaluate the activation of these areas, as well as in vivo electrophysiology techniques to detect abnormal electrical activity. The communication between PVN- CeA will be analyzed by retrograde neurotracing with glycoprotein (G)-deleted rabies virus. We will also investigate if sepsis induces changes in structure and synaptic plasticity through morphological analysis of dendritic spines and optogenetics to stimulate/ inhibit afferent neurons. Finally, we will perform in vivo studies using optogenetics and inhibition of microglial activation (with minocycline) and the consequent effects on ACTH and corticosterone secretion.
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