Project Report

The neuron has a very distinct morphology. Most neurons have three major parts to their anatomy: the soma (cell body), dendrites, and axons. The dendrites receive information from other cells, which is passed to the soma. The axon provides the output for the cell to transmit information to other cells.The axon initial segment (AIS) is the part of the axon closest to the cell body and is characterized by a high density of voltage-gated Na+ and K+ channels. It is responsible for the integration of the inputs the cell receives and the initiation of output, known as an action potential. The action potential is then propagated down the axon to the axon terminal where it is connected to other cells. Thus, any changes in the properties of the AIS may affect the overall output of the cell. A large body of evidence shows that the brain is plastic or able to change. It undergoes many changes during development and throughout life as a consequence of learning, disease, aging, and other experiences. Traditionally, plasticity has been associated with changes at the synapse, the connections between different brain cells. One form of plasticity, known as Hebbian plasticity, can be summarized by the statement ‘cells that fire together, wire together.’ However, this positive feedback mechanism would quickly lead to unsustainable levels of excitability without some form of regulation. This second form of plasticity, which provides negative feedback, is known as homeostatic plasticity. Homeostatic plasticity mechanisms keep the chemical and electrical properties of neurons within a physiological range. Like Hebbian plasticity, homeostatic plasticity has been widely studied at the synapse but very little work has been done in axons. The AIS has only recently been recognized as a target of homeostatic adaptation. To date, there are two studies which demonstrate that structural changes at the AIS can contribute to homeostatic plasticity: Kuba et al. (2010) showed that deprivation of activity in avian brainstem neurons leads to an increase in the length of the AIS, as defined by the distribution voltage-gated Na+ channels and the cytoskeletal protein AnkyrinG. These cells, compared to controls, showed altered firing properties. Grubb and Burrone (2010) showed that under conditions of chronic depolarization in vitro the AIS translocates away from the cell body. When culture conditions are returned to normal, the AIS was shown to re-translocate back towards the cell body. Together, these findings suggest that the AIS may play an important role in maintaining homeostatic firing properties in neurons. These adaptive mechanisms could play an important role in processes such as learning and memory or aging, but the extent to which neuronal circuits utilize AIS plasticity is still unknown. To address these questions, I set out to learn electrophysiology techniques to measure the electrical properties of cells in a mammalian slice and then correlate this to the length of the AIS. Since returning home, I have used Neuron (v7.1) modeling program to show that in a model of cortical neuron, changing the length of the AIS does indeed affect the firing properties of the cell. Using the electrophysiology techniques I learned while studying in Japan, I will continue to address the role of the AIS in homeostatic plasticity.

National Science Foundation (NSF)
Office of International and Integrative Activities (IIA)
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Carter Kimsey
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Baalman Kelli L
United States
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