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PhD Proposal Seminar – Miranda de Saint-Rome (Woodin Lab)

May 11, 2021 @ 1:00 pm - 1:30 pm

Characterizing hyperexcitability in the C9orf72 mouse model of ALS



Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in humans, whereby upper motor neurons in the motor cortex and lower motor neurons in the spinal cord degenerate, eventually resulting in death. A key mechanistic determinant of neurodegeneration in ALS is postulated to be aberrations in neuronal excitability and subsequent excitotoxicity in the primary motor cortex, promoting a cascade of pathological events that facilitate cell death. Additionally, previous research has identified the GGGGCC hexanucleotide repeat expansion in the C9orf72 gene as the most common genetic cause of ALS. However, little is known about the contribution of the C9orf72 gene to neuronal excitability in the primary motor cortex. Therefore, using a C9orf72 mouse model, my aims are to (1) Characterize synaptic transmission and neuronal excitability in C9orf72 mice; (2) Elucidate the mechanisms underlying changes in transmission; and (3) Assess the ability of Riluzole, a clinically approved treatment for ALS whose mechanism of action has not been completely resolved, to work synergistically with chemogenetics to rescue hyperexcitability in C9orf72 mice. Results from this study will be the first to characterize hyperexcitability using electrophysiological recordings in the cortex and hippocampus of the C9orf72 mouse, thereby revealing essential information about the neurophysiological mechanisms underlying neurodegeneration in C9orf72 ALS patients.


Tuesday, May 11th, 2021 at 1:00pm

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Meeting ID: 858 3175 4165

Host: Melanie Woodin (m.woodin@utoronto.ca)




May 11, 2021
1:00 pm - 1:30 pm
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