Speaker: Dr. Maria Cristina De Rosa
SCITEC Rome – CNR c/o Catholic University
Title: From Neuronal Ensembles to Synaptic Engrams: Using SynActive-eGRASP to Map Learning-Induced Potentiation in Defined Neural Circuits
Host researcher: Daniela Marazziti
Abstract
The idea that memories are stored as lasting physical changes in the brain dates back to Richard Semon’s introduction of the term engram in the early twentieth century. Modern activity-dependent approaches have enabled researchers to identify neuronal ensembles recruited during learning. Nevertheless, resolving the engram at the level of individual synapses—the sites where experience-dependent plasticity is thought to encode information—has remained a major challenge.
To address this limitation, we developed SA-eGRASP, a genetically encoded reporter that combines SynActive (SA) targeting with enhanced GFP Reconstitution Across Synaptic Partners (eGRASP). SynActive uses the 5′ and 3′ untranslated regions of the immediate-early gene Arc to promote the expression of a protein of interest at potentiated dendritic spines. By using SynActive to control expression of the postsynaptic component of eGRASP, SA-eGRASP produces a fluorescent signal only at synapses that both connect defined neuronal populations and undergo potentiation within a specific time window.
After validating the system, we combined SA-eGRASP with high-resolution optical imaging to generate a detailed map of potentiated hippocampal CA3–CA1 synapses following contextual fear conditioning. Its high signal-to-noise ratio also allowed us to follow the long-term structural dynamics of SA-eGRASP-positive dendritic spines. By linking circuit connectivity, synaptic potentiation, and longitudinal imaging, SA-eGRASP provides a new means of investigating the synaptic basis of memory in vivo during naturalistic behavior.