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Fear and anxiety: role of the orexinergic system in the medial prefrontal cortex


The ability to detect and predict threatening or stressful events is essential for our survival. Although recent studies have focused on mPFC as a fundamental structure in modulation of the emotionality, and the hypothalamus has also been implicated in the regulation of these processes, and the hypothalamic neuropeptide orexin (hypocretin) appears to be involved in the processing of states of fear and anxiety. In this context, it has been suggested that orexinergic neurons of the lateral hypothalamus (LH) projecting to the mPFC play an important role in the cognitive functions performed by the mPFC. However, the role of orexinergic mechanisms in the mPFC, especially the LH-mPFC pathway, during the organization of the behavioral responses associated with fear and anxiety is unknown. Therefore, using neurotracing, immunohistochemistry, neuropharmacology and optogenetic techniques associated with behavioral assays, the aims of the present study will be to investigate the role of orexinergic mechanisms in the prelimbic cortex (PL), sub-region of the mPFC, and the LH-PL pathways during the organization and expression of the defensive responses associated with fear and anxiety. Thus, our hypothesis is that orexinergic mechanisms, mainly via orexin type 1 (OX1R) receptors, are fundamental during the organization and expression of the behavioral responses associated with fear and anxiety. We expect that the present project could broaden our knowledge regarding the neurophysiology of fear and anxiety, as well as encourage the development of new drugs, especially new strategies for the treatment of psychiatric disorders. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DA SILVA, JULIANA ALMEIDA; ALMADA, RAFAEL CARVALHO; DE PAIVA, YARA BEZERRA; COIMBRA, NORBERTO CYSNE. Endocannabinoid neuromodulation in the neostriatum decreases the GABAergic striato-nigral disinhibitory function and increases the nigro-collicular inhibitory pathway activity. JOURNAL OF NEURAL TRANSMISSION, v. 127, n. 8, . (19/01713-7, 17/11855-8, 15/10313-1, 09/02458-9, 07/01174-1, 12/03798-0, 18/03898-1, 12/22681-7)
FALCONI-SOBRINHO, LUIZ LUCIANO; DOS ANJOS-GARCIA, TAYLLON; HERNANDES, PALOMA MOLINA; RODRIGUES, BRUNO MANGILI DE PAULA; ALMADA, RAFAEL CARVALHO; COIMBRA, NORBERTO CYSNE. Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic-like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice. Psychopharmacology, v. N/A, p. 17-pg., . (17/22647-7, 12/22681-7, 17/11855-8, 07/01174-1, 19/01713-7, 18/03898-1, 13/10984-8, 20/15050-7, 12/03798-0)

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