The laboratory has developed a number of new tools for imaging and analysis of light and electron microscopic images. Much of our focus is on automating tasks that have been laborious and time consuming for humans. This has required building new microtomes We are always interested in companies that wish to help develop or market these technologies.

• Generate neuronal maps ("connectomics") and investigate the mechanisms that underlie the formation of these patterns.
• Study the most accessible synapses in the peripheral nervous system in transgenic mice using new labeling strategies which permit long-term monitoring of individual nerve terminals and postsynaptic specializations during development, adult plasticity, and aging.
• Develop novel electron microscopy methods to improve our ability to resolve synaptic structure and automatically generate connectomes with the aim of eventually doing the wiring diagram of the entire brain.

Brainbow mice: A set of fluorescent protein transgenic mice whose neurons have the potential to display every color of the rainbow.  Depending on the type of analysis used, over 89-166 colors may be distinguished. This, in turn, allows the unambiguous identification and tracing of multiple cells within a neuron ensemble, a critical step toward mapping the ''connectome''. Such wiring diagrams should lead to better understanding of diseases such as autism and schizophrenia, as well as new insight into learning and other cognitive functions.

More information about Brainbow mice can be found here:

• http://news.harvard.edu/gazette/story/2007/10/researchers-create-colorful-brainbow-images-of-the-nervous-system/ 
• Brainbow mice: A technicolor approach to map the neuronal circuits

Learn more about the Connectome project at the Center of Brain Science of Harvard University.

http://cbs.fas.harvard.edu/science/connectome-project

Each human brain contains many billions of neurons connected through thousands of miles of axons at trillions of synaptic connections. The complexity is daunting and far greater in scale than any other known objects. As a precursor to an ultimate goal of a human brain map, the laboratory has begun tracing and cataloging neuronal connections in smaller animals with smaller brains. As a start, concentrating on the development and adult wiring diagram of neuromuscular junctions.

The laboratory has developed "Brainbow" transgenic animals in which each neuron is tagged with a unique color by stochastic mixing of three-four fluorescent proteins. This combinatorial XFP expression provides a way to distinguish the connectivity of many neurons of the same class and visualize the details of synaptic circuits.

To trace longer pathways that interconnect different brain regions, the lab has worked on creating a new automated process of brain sectioning onto tape, imaging by scanning electron microscopy, and computational analysis of the wiring patterns.

It is hoped that these connectional maps will be beneficial as neuroscience delves deeper into a number of fundamental but poorly understood aspects of neuroscience including: the relation between brain structure and the information stored in brains, the proximate causes of mental illness, and learning disorders, and the changes associated with aging and development. For humans, such maps would have special significance because they would represent a blueprint of ourselves, including imprints of all those things that are not in our genome, such as all the things we have learned throughout our lives.

Images of the brain produced using the Brainbow technique. See "A technicolour approach to the connectome", 2008, Nature Reviews Neuroscience 9:417-22 for more details.

Biological Mechanisms and Pathways

• Axon •
• Connectomics •
• Neuromuscular junction •
• Neuron •
• Synapse
•  

Central Nervous System

• Neural development •
• Neuromuscular junction •
• Synaptic competition
•  

Disease Mechanisms

• Autism •
• Schizophrenia
•  

Research Tools and Instrumentation

• Automated optical microscopy •
• Automation •
• Automation •
• Brainbow system •
• Computer-assisted image analysis •
• Computer-assisted image analysis •
• Computer-assisted image analysis •
• Confocal microscopy •
• Fluorescent labels •
• Microtomes •
• Scanning electron microscopy •
• Transgenic mice
•