Synaptome of a Memory

2015 Scientific Innovations Award
Kristen Harris, Ph.D.
University of Texas – Austin

A longstanding question in neuroscience concerns the cellular mechanisms of learning and memory. Since synapses were first discovered as the sites of communication between neurons, scientists have thought that changes in their number or structure would be a likely substrate of memory. Although evidence has accumulated, proof of this hypothesis has been elusive. Addressing this question requires substantial improvement in understanding how the brain is wired, namely, the “connectome”. Ultimately, the connectome will contain a map of the location and type of every synapse in the brain. The synaptome of a memory, sensation, or behavior is quite different from the connectome of a brain region because these experiences likely involve a subset of synapses distributed across different brain regions. Hence, to understand mechanisms, it is necessary to know which specific synapses were involved. Detecting synapses and their subcellular components requires the nanoscale resolution of serial section electron microscopy, an approach that has been pioneered in my laboratory. Dr. Harris’ lab proposes new strategies that will for the first time, provide specific identification of the progression and ultrastructural consequences of activity-dependent synapse remodeling in a cellular mechanism of learning and memory, a crucial first step in defining the synaptome of a memory. Nothing like this has ever been done before and the findings are crucial not only to understand the basic neuroscience and development of learning and memory, but also to illuminate synaptic dysfunction in prominent disease states, such as autism and Alzheimer’s disease.

Other Awards

James J DiCarlo, M.D., Ph.D., Massachusetts Institute of Technology
Using Computer Models of the Neural Mechanisms of Visual Processing to Non-Invasively Modulate Brain States
DiCarlo’s research team is exploring an innovative approach to address emotional challenges, such as anxiety and depression. Traditional treatments for these disorders can be complex and often cause unpleasant side effects,…
Eiman Azim, Ph.D., The Salk Institute for Biological Studies
Learning from Error: Defining how Cerebellar Circuits Drive Adaptation in a Changing World
The ability to move effectively through the world is one of the most important functions of the brain. However, the world and the body are constantly changing, meaning the signals…
Hillel Adesnik, Ph.D., University of California, Berkeley
All Optically Probing the Neural Codes of Perception in the Primate Brain
How patterns of action potentials in space and time give rise to sensory experience is among the most enduring mysteries of biology. Despite decades of experiments correlating brain activity patterns…
Chaolin Zhang, Ph.D., Columbia University
Human-specific Alternative Splicing, Brain
Development, and Ciliopathies
Like movie frames needing to be edited to tell an engaging story, pieces of genetic information stored in DNA for each gene need to be sliced and rejoined, through a…