Grant: Master's Award: Canada Graduate Scholarships

Background: Epilepsy is a brain disorder which affects over 70 million people around the world, which is characterized by a recurrence of seizures. Seizures arise from hyperexcitability in the brain, which can result from a disruption to the brain's natural balance between excitation and inhibition. When excitability gets too high, somatostatin interneuron (SOM)-mediated inhibition is recruited. We are looking at two specific genes that are linked to this response: Elfn1 (extracellular leucine rich repeat and fibronectin type III domain containing 1) and mGluR7 (metabotropic glutamate receptor 7). As such, work in other labs and preliminary work in our lab has shown that Elfn1 knockout (Elfn1 KO) mice experience seizures when they have their cages changed. As previously mentioned, seizures occur from an episode of increased brain activity and excitability; brain activity has also been shown to share a relationship with moderate changes in pH. Studies have shown that repetitive brain stimulation will moderately decrease pH levels. Our study focuses on this relationship and aims to investigate if/and how the Elfn1/mGluR7 interaction can contribute to synaptic transmission in the cortex during periods of moderate acidification.Experimental Design: Whole-cell patch clamp recordings will be taken from live brain slices from transgenic mice. To visualize SOM interneurons, we will use transgenic mice with red labelled SOM cells. Evoked excitatory postsynaptic currents (eEPSCs) will be recorded for 5 minutes in artificial cerebrospinal fluid (aCSF) at physiological pH (7.3), followed by 5 minutes at moderately acidic pH (6.7), before recovering for 5 minutes again at physiological pH.