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. We propose 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

Angelique Bordey, Ph.D., Yale University
The Role of Ribosomes in Synaptic Circuit Formation and Socio-Communicative Deficits
Our 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 with a 30-60% incidence…
Adam E. Cohen, Ph.D., Harvard University
To spike or not to spike? Mapping dendritic computations in vivo.
The brain is made of neurons, and neurons convert synaptic inputs to spiking outputs. How does a neuron decide when to spike?
Gina Turrigiano, Ph.D., Brandeis University
Homeostatic Maintenance of Neocortical Excitation-inhibition Balance by Ciliary Neuropeptidergic Signaling
Brain circuit wiring is adjusted during adolescence to generate fully functional circuits, and this process depends on an interaction between genetics and experience. During this period of experience-dependent development, excitatory…
Gregory Scherrer, Ph.D., The University of North Carolina at Chapel Hill
Mechanisms of Affective States and Drug Discovery at the Intersection of Chronic Pain and Opioid Addiction
Pain is normally a sensation that we experience when our body is exposed to damaging stimuli, such as the noxious heat of an open flame. However, when chronic, pain becomes…