Selective and Localized Marking of Activated Dendritic Spines Using a Novel Genetic Construct, Slayr

The brain's ability to store memory is as remarkable as it is complex. The mechanism behind memory storage is still not fully understood and has become an essential question in the neuroscience field. Long-term memories are thought to form via the strengthening of specific connections between neurons in the brain. At the onset of experience or event, an electrochemical signal causes an explicit circuit of neurons to display highly correlated electrical activity. When that same set of neurons is reactivated in mice, they are able to recall the original experience. However, it has been shown that one neural network can encode more than one memory. This suggests a synapse-specific memory engram model. A memory is allocated and consolidated via miniscule molecular and structural modifications that occur between the synapses of adjoining neurons. These modifications strengthen the connections between synapses and thereby form a plausible mechanism for memory storage. This ever-changing modulation of synaptic connections is known as synaptic plasticity. In order to effectively study the exact modifications that take place at the synaptic level, activated dendritic spines need to be identified. Dendritic spines are the structural correlate of excitatory synapses, and no reliable or reproducible system for this specific type of localized marking currently exists. I helped to develop a Synaptically Localized Activity Reporter (SLAyR) that will allow for the specific marking of active synapses within neurons. Three versions of SLAyR were cloned by combining a variety of different genetic elements that target the reporter to the activated synapse and mark it with a fluorescent protein. The most operative version of SLAyR will be used as a visualization tool to better elucidate the molecular mechanisms of plasticity and long-term memory consolidation.