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 contextual fear.

Objectives: We investigated the role of orexin-A (Orx) and orexin type 1 receptors (OrxR) in the PL during the expression of contextual conditioned fear in mice.

Methods: Neural tract tracing of the LH-PL pathway and OrxR immunoreactivity in the PL of C57BL/6 male mice were performed.

In Vivo Neural Tract Tracing Procedures: Unravelling Neural Hodology Using Fluorescent and Non-fluorescent Neural Tract Tracers, Optogenetic Approach, and Diffusion Tensor Neurotractography Protocols.

Fluorescent and non-fluorescent neural tract tracers enable the investigation of neural pathways in both peripheral and central nervous systems in laboratory animals demonstrating images with high resolution and great anatomic precision. Anterograde and retrograde viral tracers are important cutting-edge tools for neuroanatomical mapping. The optogenetic consists of an advanced alternative for in vivo neural tract tracing procedures, fundamentally considering the possibility to dissect and modulate pathways either exciting or inhibiting neural circuits in laboratory animals.

Neostriatum neuronal TRPV-signalling mediates striatal anandamide at high concentration facilitatory influence on neostriato-nigral dishinhibitory GABAergic connections.

Rationale: Several lines of evidence have demonstrated that the cannabinoid type 1 receptor (CB) is found in the caudate nucleus and putamen (CPu) in addition to the substantia nigra pars reticulata (SNpr). Here, we investigated the role of endocannabinoid neuromodulation of striato-nigral disinhibitory projections on the activity of nigro-collicular GABAergic pathways that control the expression of unconditioned fear-related behavioural responses elicited by microinjections of the GABA receptor selective antagonist bicuculline (BIC) in the deep layers of the superior colliculus (dlSC).

Methods: Fluorescent neural tract tracers were deposited in either CPu or in SNpr.

Ventrolateral periaqueductal gray matter integrative system of defense and antinociception.

Defensive responses are neurophysiological processes crucial for survival during threatening situations. Defensive immobility is a common adaptive response, in rodents, elaborated by ventrolateral periaqueductal gray matter (vlPAG) when threat is unavoidable. It is associated with somatosensory and autonomic reactions such as alteration in the sensation of pain and rate of respiration.

Orexin 1 and 2 Receptors in the Prelimbic Cortex Modulate Threat Valuation.

The ability to distinguish between threatening (repulsors), neutral and appetitive stimuli (attractors) stimuli is essential for survival. The orexinergic neurons of hypothalamus send projections to the limbic structures, such as different subregions of the medial prefrontal cortex (mPFC), suggesting that the orexinergic mechanism in the prelimbic cortex (PL) is involved in the processing of fear and anxiety. We investigated the role of orexin receptors type 1 (OXR) and type 2 (OXR) in the PL in such processes upon confrontation with an erratically moving robo-beetle in mice.

The modulation of striatonigral and nigrotectal pathways by CB1 signalling in the substantia nigra pars reticulata regulates panic elicited in mice by urutu-cruzeiro lancehead pit vipers.

Cannabinoid receptor type 1 (CBR) is widely distributed in the substantia nigra pars reticulata (SNpr). However, the role of CBR at the SNpr level in threatening situations is poorly understood. We investigated the role of CBR in the SNpr on the expression of fear responses in mice confronted with urutu-cruzeiro pit vipers.

Anandamide in the anterior hypothalamus diminishes defensive responses elicited in mice threatened by Epicrates cenchria constrictor serpents.

The purpose of this study was to investigate whether the panicolytic‑like effect of different doses of anandamide microinjected into the anterior hypothalamus (AH) follows the same pattern of a bell‑shaped dose‑response curve observed with the same dose treatment in dorsomedial and ventromedial hypothalamus. We investigated this assumption by administering the cannabinoid and vanilloid receptor agonist anandamide into the anterior hypothalamus of mice and exposing them to the real threatening situation by using our experimental model based on confrontations between rodents and wild snakes. Our findings showed a gradual decay of response, with a significant attenuation of the panic attack‑like responses with anandamide at the highest dose but no effect was found after anandamide at the lowest or intermediate doses.

Opposing roles of dorsomedial hypothalamic CB1 and TRPV1 receptors in anandamide signaling during the panic-like response elicited in mice by Brazilian rainbow Boidae snakes.

Rationale: The endocannabinoid system plays an important role in the organization of panic-like defensive behavior. Threatening situations stimulate brain areas, such as the dorsomedial hypothalamus (DMH). However, there is a lack of studies addressing the role of the DMH endocannabinoid system in panic-like responses.