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

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…
Jason Shepherd, Ph.D. University of Utah
Virus-like Intercellular Signaling Underlying Autoimmune Neurological Disorders
Dr. Shepherd’s lab discovered that a brain gene critical for memory and cognition, Arc, has biochemical properties like retroviruses such as HIV. Arc protein can form virus-like protein capsids that…
Yuki Oka, Ph.D., California Institute of Technology
Molecular Mechanisms of Osmolality Sensing in the Mammalian Brain
Animals constantly detect and process sensory signals to react appropriately. External sensory information (e.g., light and sound) serves as prominent environmental cues to guide behavior. On the other hand, our…
Angelique Bordey, Ph.D., Yale University
The Role of Ribosomes in Synaptic Circuit Formation and Socio-Communicative Deficits
Dr. Bordey and her lab’s proposal aims at identifying a molecular mechanism responsible for autism-like socio-communicative defects in the developmental disorder, tuberous sclerosis complex (TSC). TSC is a genetic disorder…