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| Author(s): |
Ricardo Passoni Bindi
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2022-12-14 |
| Examining board members: |
Newton Sabino Canteras;
Jackson Cioni Bittencourt;
Antonio de Pádua Carobrez;
Francisco Silveira Guimarães
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| Advisor: | Newton Sabino Canteras |
| Abstract | |
Fear is an emotion that emerges in a situation or perception of a potential threat to survival, whether direct or indirect. Researchers have studied various brain regions to understand this emotion, from the brainstem to the cerebral cortex. At the laboratory of Functional Neuroanatomy (USP), a robust anatomical relationship was observed between the periaqueductal gray area (PAG) and the cuneiform nucleus, two neighboring regions. After exposing animals to a natural predator and its scent, studies showed an increase in FOS protein expression in the cuneiform nucleus and the PAG of exposed animals. The literature also shows that dorsal PAG and cuneiform nucleus activation evoke defensive behaviors, and PAG inhibition reduces fearful behaviors in the face of a predatory threat, in addition to showing a direct relationship between electrical activity and defensive behaviors. Despite the functional and anatomical studies, there is still a lack of studies relating the cuneiform nucleus to behavioral modulation. In addition, the PAG activity pattern under increasing levels of threats was unknown. Those blind spots guided our efforts to study the cuneiform nucleus and dorsal PAG. Our observations indicate that the activity of observed dorsal PAG cells has a strong direct relationship with threat level, and the relationship with behavior is secondary. The cuneiform nucleus connects to the predatory threat circuitry, and due to the hodological and functional relationships, it acts as a caudal component of the PAG. This nucleus receives information from the hypothalamic defense system (integrating predatory cues) from the medial part of the superior colliculus (which response to looming shadows in the superior visual field). It also integrates information from the magnocellular part of the subparafascicular nucleus of the thalamus (which integrates nociceptive information) and the peripeduncular region (which integrates nociceptive and auditory information). In this way, the cuneiform nucleus occupies a privileged position to integrate a wide range of information that represents a potential threat to the individual\'s life. The cuneiform nucleus, in turn, projects to elements of the hypothalamic defense circuit and establishes a particularly dense bidirectional projection with the dorsolateral PAG. However, until now, there is not enough information about the functional role of this nucleus. To remedy this situation, the focus of this work was the functional study of the cuneiform nucleus with optogenetic stimulation and pharmacological inhibition techniques. In our study, optogenetic activation of the cuneiform nucleus promotes defensive behaviors and inhibits hunting. We also saw that inactivation of the cuneiform nucleus during exposure to the cat (predatory threat) reduces freezing behavior. (AU) | |
| FAPESP's process: | 18/00576-3 - Investigation of the neuronal activity in the different functional columns of periaqueductal gray matter in response to a predatory threat and a predatory context |
| Grantee: | Ricardo Passoni Bindi |
| Support Opportunities: | Scholarships in Brazil - Doctorate |