Tracking precisely how learning, memories are formed

Good news! Amazing stuff!

"... “This technique provides a lens into the synaptic architecture of memory, something previously unattainable in such detail,”  ...

In their new paper, the team detailed their new technique, dubbed Extracellular Protein Surface Labeling in Neurons (EPSILON), which focuses on mapping the proteins vital for the transmission of signals across synaptic connections in the brain.

These specific proteins are called AMPARs and are considered key players in synaptic plasticity, the process that allows the brain to adapt and reorganize itself in response to new information.

Utilizing sequential labeling with specialized dyes, EPSILON enabled the researchers to monitor these proteins’ movements at high resolutions. Traditionally, understanding such detailed microscopic phenomena has required more invasive methods. Using EPSILON to observe AMPARs’ behavior in neurons represents a significant scientific advance. ...

“Our most important breakthrough is our method that can map the past history of the synthetic plasticity in the living brain ...

“By mapping the synaptic plasticity over time at multiple time points, we can truly map the dynamics of the synapses,” ... “We’ll also be able to apply this to different kinds of memories that have different patterns of synaptic plasticity.” ..."

From the abstract:

"A tool to map changes in synaptic strength during a defined time window could provide powerful insights into the mechanisms of learning and memory.

Here we developed a technique, Extracellular Protein Surface Labeling in Neurons (EPSILON), to map α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) exocytosis in vivo by sequential pulse-chase labeling of surface AMPARs with membrane-impermeable dyes.

This approach yields synaptic-resolution maps of AMPAR exocytosis, a proxy for synaptic potentiation, in genetically targeted neurons during memory formation. In mice undergoing contextual fear conditioning, we investigated the relationship between synapse-level AMPAR exocytosis in CA1 pyramidal neurons and cell-level expression of the immediate early gene product cFos, a frequently used marker of engram neurons. We observed a strong correlation between AMPAR exocytosis and cFos expression, suggesting a synaptic mechanism for the association of cFos expression with memory engrams.

The EPSILON technique is a useful tool for mapping synaptic plasticity and may be extended to investigate trafficking of other transmembrane proteins."

Tracking precisely how learning, memories are formed — Harvard Gazette "New technique may offer insights for new therapies to treat disorders like dementia"

EPSILON: a method for pulse-chase labeling to probe synaptic AMPAR exocytosis during memory formation (no public access)

EPSILON: a method for pulse-chase labeling to probe synaptic AMPAR exocytosis during memory formation (ResearchGate, open access)

EPSILON tags freshly exposed AMPARs