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Brown Researcher (A15)

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orthodromically down the axon and into its terminals. Ectopic action potentials (EAPs), however, initiate more distally (further from the cell body) on the axon and travel both orthodromically and antidromically, up the axon and into the soma. EAPs have been observed in pyramidal cells, the most common type of cortical cell, under pathological conditions such as epilepsy models and in cases of nerve trauma. Our lab recently found that a majority of pyramidal cells—the most common neural cell type in the neocortex—can fire EAPs in vitro under nonpathological conditions, which had never been seen before. To better understand this discovery, this project aims to determine the exact mechanism underlying EAP generation in pyramidal cells. We performed in vitro whole-cell patch clamp recordings in the current clamp configuration on Layer 2/3 pyramidal cells in the orbitofrontal cortex of mouse brain slices. To elicit EAPs, current steps were titrated to each cell (1000-2500 pA for 1-5 ms) until the cell fired AIS-APs for at least 80% of injections. Those pulses were delivered at 60 Hz or 100 Hz frequency. If EAPs were successfully induced, a drug or condition was added to the bath and the 60 or 100 Hz protocol was tested again. If a drug or condition affects the probability, rate, or size of EAP firing, then its target is likely to contribute to EAP generation. So far, we have tested the drug ZD7288, an HCN channel blocker, and we hope to test 11 other conditions in the coming months. Understanding the mechanism behind pyramidal EAP generation will be crucial to understanding and treating conditions like epilepsy and neuropathic pain that incorporate EAPs into their pathology. 18 Adin Pepper Fox:

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Brown / Summer Research Assistant (Neuroscience)

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Brown Researcher (A15)