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PhD Proposal Exam – Sahara Khademullah (Woodin lab)
April 21, 2016 @ 12:10 pm - 1:10 pm
PhD Proposal Exam
Thursday April 21st, 12:10 pm – Ramsay Wright Building, Rm. RW432
Sahara Khademullah (Woodin lab)
“Inhibitory Synaptic Transmission and KCC2 Function in the Motor Cortex of the Presymptomatic ALS Mouse“
Abstract
A balance between synaptic excitation and inhibition is essential for normal brain function. When this delicate balance is disrupted, it can lead to neuronal hyperexcitability, resulting in alterations in neuronal network activity and the onset of various neurological disorders, such as epilepsy, autism spectrum disorder and schizophrenia. Recent studies have shown the presence of an imbalance between excitation and inhibition in amyotrophic lateral sclerosis (ALS) as well. Thus, there is an intense need to determine how this equilibrium is maintained and what triggers its disarray. ALS (a.k.a. ‘Lou Gehrig’s disease’) is a fatal neurodegenerative disease characterized by rapid progressive muscle weakness and atrophies that affects both upper and lower motor neurons. Following the initial onset of symptoms, approximately 50% of cases are fatal within the first 1.5 years and in about 20% of the remaining cases, the disease persists for approximately 5 to 10 years until the patient dies. Recent studies performed in the SOD1G93A familial mouse model of ALS have observed reductions in KCC2 membrane expression, a key regulatory protein of inhibition, in spinal cord motor neurons. Similar studies in the SOD1G93A mouse model have also found an increase in network hyperexcitability in presymptomatic cultured spinal cord motor neurons. Thus, the focus of my PhD project is to determine if hyperexcitability in the primary motor cortex (PMC), where many patients with ALS present predominant neurodegeneration, results in a reduction in the strength of inhibitory synaptic transmission. I will also investigate whether this reduction in synaptic inhibition is associated with KCC2 expression. Evidence from this study may provide novel insights into the pathogenesis of ALS.
Ramsay Wright is a wheelchair accessible building.