ProfessorRichelle Mychasiuk

Project Opportunities

Title: Understanding the Neurobiological Underpinnings of Empathy for Pain

Summary of opportunity:

This project will use rodent models to explore the neurobiological processes that drive empathy for pain in others, and whether and how these change across the lifespan. We are particularly interested in understanding if early life trauma / adversity modifies these neurobiological processes to render certain individuals less capable of exhibiting empathy.

Opportunity synopsis:

The World Health Organization has described adverse childhood experiences (ACEs) as being the most common, intense, and disabling stressors of childhood. Although the mechanisms are not fully elucidated, ACEs modify brain development, structure, and function which leads to alteration and reorganization of many neural circuits and neurological processes. Therefore, we will use established models of early adversity (to mimic resource scarcity and early life neglect) in conjunction with complex behavioral protocols to identify individual rats that exhibit high and low levels of empathy for conspecifics who exhibit pain. We will then use advanced imaging techniques (fMRI), RNAscope, tract tracing procedures, and immunohistochemical protocols to interrogate the neurobiology of empathy for pain. These experiments will be completed across developmental stages, i.e., childhood, adolescence, adulthood, and senescence.

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Project Opportunities

Title: Investigating the Role of the Vestibular System in Circadian Rhythms

Summary of opportunity:

Mammalian biological rhythms are synchronized to the environmental light/dark cycle through a primary circadian clock in the brain. This clock receives light input from the retina to then communicate to the rest of the brain and body what the time in the external world is. From this information the clock synchronizes internal circadian rhythms to the outside world to optimise physiological functioning. This synchronization is vitally important to human health, as it includes the sleep/wake cycle.  There is also some evidence that stimuli other than light, including exercise, can reset the circadian clock, meaning these stimuli can alter the timing of circadian rhythms. These stimuli are collectively referred to as "non-photic" stimuli. Recently, evidence has emerged that the vestibular system, the sensory system responsible for our sense of balance, plays a direct role in sleep and can influence the circadian clock. This project will investigate the role that the vestibular system plays in circadian rhythms.

Opportunity synopsis:

Our general experimental model will use rats. We will monitor circadian rhythms and perform behavioural manipulations to determine if activation of the vestibular system is able to reset the circadian clock. We will use brain injections to specifically activate vestibular neurons. We will specifically show that activation or deactivation of vestibular neurons can influence circadian rhythms and determine the pathways in the brain through which this occurs. This work will have important implications for sleep and health and provide valuable information on the least known sensory system.

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Project Opportunities

Title: The Effects of Orexin Modulation on Sleep, Glymphatic Function, and Chronic Pain in Adolescence

Summary of opportunity:

The system that is responsible for the clearance of macroscopic waste from the central nervous system is the glymphatic system. This waste removal system is radically inhibited during wakefulness, being 90% more active during sleep. The implications are astounding considering that sleep disturbances are regularly reported by chronic pain patients. The bi-directional relationship between chronic pain and sleep problems could possibly explain the heightened neurodegenerative risk detected in epidemiological studies. The primary role of the neuropeptide orexin is to increase arousal levels and maintain wakefulness, thereby regulating the sleep-wake cycle. ORX-A is a nonselective agonist for the orexin receptors and is often used to treat narcolepsy; when ORX-A is administered sleep should be impaired, further limiting glymphatic function. Conversely, Suvorexant (SUV), a dual orexin receptor antagonist, is an FDA-approved drug that is administered orally for the treatment of insomnia. SUV inhibits binding of orexin A and B, thereby improving sleep. The specific purpose is therefore to examine sleep and glymphatic function in rats with chronic pain and determine whether or not short- and long-term neurological dysfunction is exacerbated when an orexin agonist is administered and ameliorated when an orexin antagonist is administered.

Opportunity synopsis:

Our general experimental model will use established models of chronic pain in adolescent male and females rats. Following therapeutic administration of the pharmacologics, we will use telemetry (sleep monitoring systems), complex behavioral tests, and tract tracing procedures, to interrogate the neurobiological changes that have occurred within sleep and pain brain systems. We will then a variety of tools, such as, advanced imaging techniques (fMRI), RNAscope, and immunohistochemical protocols to examine the mechanisms driving improvement or exacerbation of sleep and pain dysfunction.