Development of Computational Methods to Analyze Mitochondrial Calcium Signals in Astrocytes
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Date
2022-04-19
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Abstract
Astrocytes are the most abundant non-neuronal cells in the brain. Up until recent years, these cells had been thought to serve merely as supporting cells for neurons. However, recent studies have shown astrocytes can modulate neuronal function. Astrocytes can accomplish this function due to their complex morphology, a round cell soma from which thick branches, that further subdivide into thinner and more numerous branchlets, emerge. These fine processes allow each astrocyte to contact up to 100,000 neurons in the mouse brain. Therefore, studying these cells has become of utmost importance to comprehend the effects they have on neurons and overall brain health. Unlike neurons, astrocytes are not electrically excitable; instead, each astrocyte displays a panorama of calcium signals. These calcium signaling events allow astrocytes to sense and respond to neuronal signals and modulate synapses. As vital as the study of these calcium signals is, their analysis is extremely time consuming and inefficient. Current programs that enable automated analysis of calcium signals tend to focus on neuronal firing since it is less sporadic and more rhythmic. Astrocytic signals, on the other hand, are random and harder to characterize. To solve this problem, we generated Measurement of Astrocytic Related Signals (M.A.R.S.), a MATLAB based computational program that looks at preselected regions of interest (ROIs), and classifies events, or significative calcium peaks. After event selection, the program measures each event’s amplitude, duration, and frequency. These measurements allow us to look at the kinetics and location of Ca2+ signals in astrocytes. Since a significant portion of astrocytic calcium signals are found in mitochondria, this study particularly focuses on calcium signals within the mitochondria of astrocytes. In summary, our MATLAB based astrocyte calcium analyzer will impact the way we study astrocytes, understand their function, and view the role they play in the brain’s overall health.
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Astrocytes, Calcium signaling, analysis