MSc Exit Seminar – Dillon McKenna (Peever lab)

MSc Exit Seminar

Thursday January 12^th, 12:10 pm – Earth Sciences Centre, Rm. 3087

Dillon McKenna (Peever lab)

“Transduction of human alpha synuclein in the subcoeruleus region causes symptoms of REM sleep behaviour disorder in mice“

Abstract

During rapid eye movement (REM) sleep, vivid dreams and wake-like cortical activity are accompanied by skeletal muscle paralysis (atonia) interspersed with phasic twitches. The motor characteristics of REM sleep are thought to be controlled by the pontine subcoeruleus (SubC) region. REM sleep behaviour disorder (RBD) is a disruption of motor control during REM sleep, which manifests as a loss of atonia, increased phasic twitches, and overt movements. Understanding the development of RBD is vital, as >90% of RBD patients eventually develop some form of synucleinopathy, a neurodegenerative disorder associated with toxic aggregates of the protein alpha-synuclein (αSyn), most commonly Parkinson’s disease. While the brains of RBD patients show αsyn aggregates within the SubC region, there is currently no direct evidence of the effects that SubC αSyn-related pathology will have on the characteristics of REM sleep. Using targeted overexpression of human αSyn in the SubC region, I have demonstrated αSyn aggregation, excessive muscle twitches during REM sleep, and slowing of cortical activity arise in wild type mice. This project demonstrates, for the first time, a direct link between the emergence of RBD symptoms and pathological αSyn in the SubC region, and has produced an animal model of RBD that is clinically relevant to the underlying pathology seen in the human disease.