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The Axon Initial Segment (AIS) is a compartment within the neuron that plays a major role in the initiation of action potentials. Changes to AIS length and position can alter the probability of action potential firing. A majority of modeling studies consider the AIS to have linear morphology; however, we have observed different AIS shapes in different pathological conditions.
The objective of this research is to classify AISs by shape (straight, curved, or kinked) and to determine the frequency of each shape across normal and pathological conditions.
We stained AISs in cortical tissue using immunohistochemistry and imaged them with a confocal microscope. After imaging, we qualitatively categorized AISs in normal and pathological samples based on their shape and plotted them in ImageJ to obtain numerical data (Cartesian coordinates).
We have compared AISs in cortical tissue from wild type mice to those from the Mecp2+/- model of Rett syndrome. We plan to use the Cartesian data to develop a model that describes the linear and non-linear morphologies of the AIS.
Although previous research has demonstrated that position, composition, and length of AISs helps determine neuronal excitability, the relationship between AIS shape and pathology has not been examined. The current study helps establish AIS morphology as a possible pathological feature that may have functional consequences, and future experiments will investigate a relationship between AIS shape and neuronal excitability. Additional research may help to gain a deeper understanding of normal and pathological development and may lead to the development of new treatments.
Axon initial segment (AIS); AIS morphology; Rett syndrome; Mecp2+/- model
Garcia-Trujillo, Betsua and Hines, Rochelle Ph.D., "Morphology of Axon Initial Segments under Normal and Pathological Conditions" (2021). Undergraduate Research Symposium Posters. 40.