Carnegie Mellon University researchers have developed a new approach to broadly survey learning-related changes in synapse properties. In a study published in the Journal of Neuroscience and featured on the journal's cover, the researchers used machine-learning algorithms to analyze thousands of images from the cerebral cortex. This allowed them to identify synapses from an entire cortical region, revealing unanticipated information about how synaptic properties change during development and learning. The study is one of the largest electron microscopy studies ever carried out, evaluating more subjects and more images than prior researchers have attempted.

As the brain learns and responds to sensory stimuli, its neurons make connections with one another. These connections, called synapses, facilitate neuronal communication, and their anatomic and electrophysiological properties contain information vital to understanding how the brain behaves in health and disease. Researchers use different techniques, including electron microscopy, to identify and analyze synapse properties. While electron microscopy can be a useful tool for reconstructing neural circuits, it is also data and labor intensive. As a result, researchers have only been able to use it to study small, targeted areas of the brain until now.

Studying a large section of the brain using traditional electron microscopy techniques would result in terabytes of unwieldy data, given that the brain has billions of neurons, each with hundreds to thousands of synaptic connections. The new technique developed at Carnegie Mellon simplifies this problem by combining a specialized staining process with machine learning.

The technique uses a special chemical preparation that deeply stains the synapses in a sample of brain tissue. When the tissue is imaged using an electron microscope, only the synapses can be seen, creating an image that can be easily classified by a computer program. Researchers then use machine learning algorithms to identify and compare synapse properties across a column of the cerebral cortex.

To test the effectiveness of their technique, the researchers examined how synapses across a complex circuit, composed of hundreds of interconnected neurons, would change with altered somatosensory input. The researchers analyzed close to 25,000 images and 40,000 synapses, exponentially more than they were ever able to look at before using traditional methods.

They found that the technique could be used to determine increases in synapse density and size during development and learning. Most notably, they found that synapse properties changed in a coordinated way across the entire region of the neocortex examined.

The researchers are now beginning to use this data to develop new hypotheses about how synapses are organized in the neocortex in response to sensory input.

http://www.cmu.edu/news/stories/archives/2015/december/synaptic-density.html