Neural Circuits at a Cellular Level

Neural Circuits at a Cellular Level

Researchers at the Allen Institute for Brain Science are creating detailed, publicly available atlases of the behavior of neurons in the mouse brain, following this standardized data collection pipeline.

Overview

Advances in neuroscience over the past decade have enabled researchers to examine the neural circuitry of the brain at unprecedented resolution. Furthermore, open access to large-scale, publicly available atlases that provide an extensive catalog of cell structure, connectivity, and neural activity in response to standardized stimuli, promises to accelerate new discoveries of the function of this neural circuitry. This unit explores the work of the Allen Institute for Brain Science on the creation of brain observatories, and the critical role of connectomics in mapping neural connectivity.

Videos

Christof Koch describes research at the Allen Institute for Brain Science aimed at building a comprehensive online catalog of the many types of cell that exist in human and mouse brains, based on detailed studies of cell morphology, electrophysiology, and transcriptomics. Even in the mouse brain, there are about 1,000 different cell types. This catalog will aid research on neurological diseases that afflict only a limited subset of these cell types.
The Allen Brain Observatory provides the first comprehensive in vivo survey of the physiological activity of neurons in the mouse visual cortex, following a standardized data collection pipeline. Christof Koch describes the motivation behind this large-scale open science project, and highlights some of the scientific discoveries that have emerged from modeling studies using these data.
Michael Buice presents a tutorial on the Allen Software Development Kit (SDK) that provides software to read and process data in the Allen Brain Atlases that include the Allen Cell Types Database, Mouse Connectivity Atlas, and Allen Brain Observatory. The tutorial incorporates sample tasks involving the processing and visualization of this data.
The mammalian visual system, from the retina to neocortex, has been studied extensively at the anatomical and functional levels, but direct observation of cellular-level functional interactions across multiple levels of the hierarchy has been lacking, due to the challenge of simultaneously recording activity across levels. Christof Koch describes part of the Allen Brain Observatory dataset, that surveys spiking from tens of thousands of neurons in six cortical and two thalamic regions in the mouse, responding to a battery of visual stimuli.
Connectomics aims to construct a complete map of the detailed synaptic connections between neurons. Jeff Lichtman takes a historical journey through the evolution of methods to visualize neural connections at a synaptic level, and key discoveries of how neural connectivity changes during early development. Competitive interactions between neurons that innervate the same target cell result in a sharpening of patterns of neural connections, which may be important in learning and the formation of memories.

Further Study

Online Resources

Additional information about the speakers’ research and publications, and the Allen Institute, can be found at these websites:

Extensive resources are available at the Allen Institute for Brain Science website, including the Allen Brain Observatory, the Allen SDK, and the Brain Modeling Toolkit.

Readings

Billeh, Y. N., Cai, B., [..;], Arkhipov, A. (2020) Systematic integration of structural and functional data into multi-scale models mouse primary visual cortex, Neuron, 106(3), 388-403

Dai, K., Gratiy, S. L., [...]. Arkhipov, A. (2020) Brain Modeling Toolkit: An open source software suite for multiscale modeling of brain circuits, PLoS Computational Biology, 16(11), e1008386

de Vries, S. E. J., Lecoq, J. A., [...], Koch. C. (2020) A large-scale standardized physiology survey reveals functional organization of the mouse visual cortex, Nature Neuroscience, 23, 138-151

Gouwens, N. W., Sorensen, S. A., [...], Koch, C. (2019) Classification of electrophysiological and morphological neuron types in the mouse visual cortex, Nature Neuroscience, 22, 1182-1195

Kasthuri, N. Hayworth, K. J., [...], Lichtman, J. W. (2015) Saturated reconstruction of a volume of neocortex, Cell, 162(3), 648-661

Nandi, A., Chartrand, T., [...], Anastassiou, C. A. (2020) Single-neuron models linking electrophysiology, morphology and transcriptomics across cortical cell types, bioRxiv, April 10, 2020

Siegle, J. H., Jia, X., [...], Koch, C. (2021) Survey of spiking in the mouse visual system reveals functional hierarchy, Nature, 592, 86-92

Swanson, L. W., Lichtman, J. W. (2016) From Cajal to connectome and beyond, Annual Review of Neuroscience, 39, 197-216

Tapia, J. C., Wylie, J. D, [...], Lichtman, J. W. (2012) Pervasive synaptic branch removal in the mammalian neuromuscular system at birth, Neuron, 74(5), 816-829