Orexin mechanisms in the prelimbic cortex modulate the expression of contextual conditioned fear
Rationale: Despite the existing anatomical and physiological evidence pointing to the involvement of orexinergic projections from the lateral hypothalamus (LH) in regulating fear-related responses, little is known regarding the contribution of the orexin system in the prelimbic cortex (PL) on contex...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | Brasil |
| Institución: | Universidade Estadual Paulista (UNESP) |
| Repositorio: | Repositório Institucional da UNESP |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unesp.br:11449/299213 |
| Acceso en línea: | http://dx.doi.org/10.1007/s00213-024-06701-x https://hdl.handle.net/11449/299213 |
| Access Level: | acceso abierto |
| Palabra clave: | Contextual fear conditioning Medial prefrontal cortex Orexin type 1 receptor Orexin-A Prelimbic cortex |
| Sumario: | Rationale: Despite the existing anatomical and physiological evidence pointing to the involvement of orexinergic projections from the lateral hypothalamus (LH) in regulating fear-related responses, little is known regarding the contribution of the orexin system in the prelimbic cortex (PL) on contextual fear. Objectives: We investigated the role of orexin-A (OrxA) and orexin type 1 receptors (Orx1R) in the PL during the expression of contextual conditioned fear in mice. Methods: Neural tract tracing of the LH-PL pathway and Orx1R immunoreactivity in the PL of C57BL/6 male mice were performed. In a pharmacological approach, the animals were treated with either the Orx1R selective antagonist SB 334,867 (3, 30, and 300 nM/0.1 µL) or OrxA (28, 70, and 140 pmol/0.1 µL) in the PL before the test session of contextual fear conditioning. Results: Neural tract tracing deposits in the LH showed some perikarya, mainly axons and terminal buttons in the PL, suggesting LH-PL reciprocate pathways. Furthermore, we showed a profuse network comprised of Orx1R-labeled thin varicose fibers widely distributed in the same field of LH-PL pathways projection. The selective blockade of Orx1R with SB 334,867 at 30 and 300 nM in the PL caused a decrease in freezing response, whereas the treatment with OrxA at 140 pmol promoted an increase in freezing response. Conclusion: In summary, these data confirmed an anatomical link between LH and PL, established the presence of Orx1R in the PL, and a modulatory role of the orexin system in such structure, possibly mainly via Orx1R, during contextual fear conditioning. |
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