Linking Macroscopic with Microscopic Neuroanatomy Using Synthetic Neuronal Populations

Abstract

Dendritic morphology has been shown to have a dramatic impact on neuronal function. However, population features such as the inherent variability in dendritic morphology between cells belonging to the same neuronal type are often overlooked when studying computation in neural networks. While detailed models for morphology and electrophysiology exist for many types of single neurons, the role of detailed single cell morphology in the population has not been studied quantitatively or computationally. Here we use the structural context of the neural tissue in which dendritic trees exist to drive their generation in silico. We synthesize the entire population of dentate gyrus granule cells, the most numerous cell type in the hippocampus, by growing their dendritic trees within their characteristic dendritic fields bounded by the realistic structural context of (1) the granule cell layer that contains all somata and (2) the molecular layer that contains the dendritic forest. This process enables branching statistics to be linked to larger scale neuroanatomical features. We find large differences in dendritic total length and individual path length measures as a function of location in the dentate gyrus and of somatic depth in the granule cell layer. We also predict the number of unique granule cell dendrites invading a given volume in the molecular layer. This work enables the complete population-level study of morphological properties and provides a framework to develop complex and realistic neural network models.

Author Summary

Computational models of neurons and neural networks provide a valuable avenue to test our understanding of brain regions and to make predictions to guide future experimentation. Each neuron has a unique dendritic tree, features of which can vary depending on the location of the neuron within the particular brain region. In this study, we generated a complete population of dendritic trees for the most numerous type of neuron in the hippocampus, the dentate gyrus granule cell, using a realistic three-dimensional structural context to drive the generation process. Morphological properties can now be studied at the level of complete neuronal populations, and this work provides a foundation to build upon in the construction of large-scale, data-driven neuroanatomical and network models.