Abstract
The connectomic analyses of large-scale volumetric electron microscope (EM) images enable the discovery of hidden neural connectivity. While the technologies for neuronal reconstruction of EM images are under rapid progress, the technologies for synapse detection are lagging behind. Here, we propose a method that automatically detects the synapses in the 3D EM images, specifically for the mouse cerebellar molecular layer (CML). The method aims to accurately detect the synapses between the reconstructed neuronal fragments whose types can be identified. It extracts the contacts between the reconstructed neuronal fragments and classifies them as synaptic or non-synaptic with the help of type information and two deep learning artificial intelligences (AIs). The method can also assign the pre- and postsynaptic sides of a synapse and determine excitatory and inhibitory synapse types. The accuracy of this method is estimated to be 0.955 in F1-score for a test volume of CML containing 508 synapses. To demonstrate the usability, we measured the size and number of the synapses in the volume and investigated the subcellular connectivity between the CML neuronal fragments. The basic idea of the method to exploit tissue-specific properties can be extended to other brain regions.
Highlights
Cajal’s neuron doctrine was proven correct by the experiments in the late 1950s to 1960s, which directly observed the synapses with electron microscope (EM) (Gray, 1959; Colonnier, 1968)
The volume of the test set (11.9 μm × 11.9 μm × 12.4 μm) is 0.15% of the entire data. It contains 598 neuronal fragments in total, which consist of 574 parallel fiber (PF), 4 Purkinje cell (PC), 17 INs, and 3 climbing fiber (CF) (Figure 3A)
About 57.6% of voxels of the volume belong to reconstructed neuronal fragments, and the chief proportion of the remaining voxels belong to glial cells
Summary
Cajal’s neuron doctrine was proven correct by the experiments in the late 1950s to 1960s, which directly observed the synapses with EM (Gray, 1959; Colonnier, 1968). Thanks to the advancement in molecular biology and optics, various methods to observe the synapses such as genetic labeling or immunochemical staining in combination with high-resolution light microscopes (LMs) are widely used (Ippolito and Eroglu, 2010; del Valle Rodríguez et al, 2011). For the connectomics, whose ambition is to map the complete wiring diagram of nervous systems, EM is, presently, the only available solution since all the neurons and synapses in a nerve tissue are homogeneously imaged in EM (Denk and Horstmann, 2004). The connectome of a nematode, C. elegans, still remains the only complete connectome (White et al, 1986).
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