The role of the orexinergic system in the medial prefrontal cortex in the expression of contextual conditioned fear

Abstract

The ability to detect and predict threatening or stressful events is essential for survival. The medial prefrontal cortex (mPFC) has been the target of several studies in neuroscience since the participation of this structure in mnemonic processes and in the control of emotions is investigated. The hypothalamus has also been implicated in the regulation of such processes, and the hypothalamic orexin neuropeptide (hypocretin) appears to be involved in the regulation of fear and anxiety. Recent studies have associated the orexinergic system (hypocretin) with the neurobiology of emotions, especially in the regulation of behaviors associated with fear and anxiety. However, little is known regarding the role of orexinergic mechanisms in mPFC during the organization of behavioral responses associated with fear and anxiety. The present work aims to investigate the role of orexinergic mechanisms in the pre-limbic cortex (PL), mPFC sub-region, during the organization and expression of defensive responses associated with conditioned fear. In this scenario, the role of orexinergic mechanisms in PL during the organization and expression of fear conditioned to the context will be investigated. First, the mice will receive microinjections of orexin-1 receptor antagonist (OX1R), in different doses, in the PL and, after they will be submitted to the experimental model of contextual conditioned fear. The hypothesis is that orexinergic mechanisms via OX1R are fundamental during the organization and expression of behavioral responses associated with conditioned fear.