Automated Neuron Shape Analysis from Electron Microscopy

Morphology based analysis of cell types has been an area of great interest to the neuroscience community for several decades. Recently, high resolution electron microscopy (EM) datasets of the mouse brain have opened up opportunities for data analysis at a level of detail that was previously impossible. These datasets are very large in nature and thus, manual analysis is not a practical solution. Of particular interest are details to the level of post synaptic structures. This paper proposes a fully automated framework for analysis of post-synaptic structure based neuron analysis from EM data. The processing framework involves shape extraction, representation with an autoencoder, and whole cell modeling and analysis based on shape distributions. We apply our novel framework on a dataset of 1031 neurons obtained from imaging a 1mm x 1mm x 40 micrometer volume of the mouse visual cortex and show the strength of our method in clustering and classification of neuronal shapes.

Probabilistic Fluorescence-Based Synapse Detection

Brain function results from communication between neurons connected by complex synaptic networks. Synapses are themselves highly complex and diverse signaling machines, containing protein products of hundreds of different genes, some in hundreds of copies, arranged in precise lattice at each individual synapse. Synapses are fundamental not only to synaptic network function but also to network development, adaptation, and memory. In addition, abnormalities of synapse numbers or molecular components are implicated in most mental and neurological disorders. Despite their obvious importance, mammalian synapse populations have so far resisted detailed quantitative study. In human brains and most animal nervous systems, synapses are very small and very densely packed: there are approximately 1 billion synapses per cubic millimeter of human cortex. This volumetric density poses very substantial challenges to proteometric analysis at the critical level of the individual synapse. The present work describes new probabilistic image analysis methods for single-synapse analysis of synapse populations in both animal and human brains.