Extreme Neuroanatomy

Table of Contents

Movies of Lathe Microtome cutting and tape collection in action!

SBPSL Full PowerPoint Presentation (Warning large file! *.ppt file is 29Mbytes)

Movie: Piloting down a virtual neuron's dendritic tree using "Dendritic Explorer" test program (49 Second *.avi file, 22 Mbytes)

Dendritic Explorer test program overview slide

Contacts

Extreme Neuroanatomy: Toward a Sparse Synapse-Resolution Brain Connectivity Atlas of the Human Brain


Figure 1: Shows how a Single Brain Physical Slice Library Infrastructure (an online, collaborative neuroanatomical tracing experiment) could facilitate the creation of a Sparse Synapse-Resolution Brain Connectivity Atlas.	Figure 2: Shows what we believe to be the key enabling technology needed to make a Single Brain Physical Slice Library possible: an Automatic Taping Lathe-Microtome.

NOTE: This website is out of date. Please link to http://www.mcb.harvard.edu/lichtman/ATLUM/ATLUM_web.htm for the most recent results of the Automatic Tape Collecting Lathe Ultramicrotome I am currently building at Harvard University.

Neuroscientists today are routinely carrying out evermore-advanced physiological experiments (single cell recordings, functional imaging, etc.) and cognitive scientists are proposing and testing evermore-comprehensive cognitive models (both at the neuronal and systems levels). Unfortunately, these experiments and models involve brain systems where incomplete information regarding the system’s underlying neural circuitry presents one of the largest barriers to research success. It is widely accepted that what is needed is a comprehensive and reliable wiring diagram of the brain that will provide a neuroanatomical scaffolding (and a set of foundational constraints) for the rest of experimental and theoretical work in the neuro- and cognitive sciences. Unfortunately, the current approach of attempting to integrate the deluge of thousands of individual neuroanatomical tracing experiments into a coherent whole (even when using the neuroinformatic database tools of the Human Brain Project) is proving to be an incredibly daunting task.

There is an alternative approach, one that avoids the problem of stitching together the results of thousands of disparate experiments. The imaging of a single brain at a sufficiently high resolution, while maintaining registration across size-scales, would allow direct tracing (without tracer chemicals) of neural processes and synaptic connections. Specialized researchers using the raw data in such a Synapse-Resolution Brain Connectivity Atlas could map all the regions, axonal pathways, and synaptic circuits of the brain. Unlike separate specialized experiments, the results would immediately and easily be integrated because they are all performed on the same physical brain.

Today, the creation of such a synapse-resolution atlas has only been achieved for tiny invertebrate animals such as C. Elegans, and for small pieces of the vertebrate retina. Such examples, however, serve as proof that the fundamental technologies (most notably serial section electron microscopic 3D reconstruction) already exist. The challenge is in extending these imaging technologies to map structures that are 1x10⁵ (mouse brain) and 1x10⁸(human brain) times as large as C. Elegans.

Research groups actively seeking to extend synapse-resolution imaging to whole vertebrate brains and groups developing the software algorithms necessary to analyze the resulting raw data (in order to map all brain regions, axonal pathways, and neuronal circuits) are engaged in what we call “extreme neuroanatomy” research. This web site is dedicated to providing links to this growing research community’s work and to highlighting the importance of this work to the larger neuroscience community.

The main goals of this website are:

	To explicitly emphasize the importance of Synapse-Resolution Brain Connectivity Atlases to the neuroscience and cognitive science fields, and to argue for their technological feasibility.
	To highlight the need for basic research into imaging instrumentation, microtome design, and algorithm development enabling such an atlas’ creation and use.
	To foster collaboration between disparate research groups by providing links to their research and by highlighting the importance of their work in the context of creating Synapse-Resolution Brain Connectivity Atlases.

Other goals of this website are:

	To propose a more feasible (i.e. lower-budget) route to the creation of a Sparse Synapse-Resolution Brain Connectivity Atlas through the creation of an online collaborative neuroscience imaging experiment called a Single Brain Physical Slice Library.
	To present our own research into the design and construction of an Automatic Taping Lathe Microtome, and our research into voxel-based automatic neuronal process tracing algorithms.

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Last Updated: 03/16/2007