Realistic 3D Reconstructions of MSNs Through Computational Methodologies

Lecture Centre Concourse

Structural and functional changes in neurons are of paramount importance in neurological, neuropsychiatric, and neurodegenerative diseases. Computer models aid in determining how these changes shape the firing output of neurons. Here we use computational tools to derive information on the 3D morphology of neurons. We focus on striatal neurons, which control movement execution and reward. We show that the morphology of striatal neurons expressing D1 dopamine receptors is altered in mice that carry a genetic mutation also found in humans affected by OCD. These 3D reconstructions are obtained using software that takes into account the volumetric and spatial properties of single medium spiny neurons (MSNs). Reconstruction data was used to look at the measured structural changes involved in the loss of the glutamate transporter, EAAC1. We used Simple Neurite Tracer (SNT), a plugin available from Fiji by ImageJ, to create a visual representation of these changes by processing a stack of 2D confocal microscopy images into volumetric reconstructions. By using Tubular Geodesics, an SNT add on, we took tubularity measurements of neuronal branches. NEURON, a simulation software, then analyzed the trace files to give the MSNs physiological properties. Through neuronal models, we can relate the influence of EAAC1 to the changes that take place in synaptic transmission through individual MSNs. Simulating reconstruction data can provide valuable information on any neuronal abnormalities that may be present in a given cell. We hope that the data collected can help unveil the underlying physiological questions on EAAC1’s role in hyperactivity and OCD.