Arc-driven mGRASP highlights CA1 to CA3 synaptic engrams

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Cellular engrams are neuronal subpopulations crucial for memory encoding and recall.
• Synaptic connections between engram neurons, termed synaptic engrams, are vital memory substrates.
• Labeling synaptic engrams requires targeting pre- and postsynaptic compartments of engram neurons.

Purpose of the Study:

• To explore the transsynaptic GFP reconstitution system (mGRASP) for labeling synaptic engrams.
• To compare the efficiency of mGRASP using different immediate-early gene (IEG) promoters (Arc and cFos) in hippocampal neurons.
• To characterize the expression of cellular and synaptic labels in response to environmental exposure and memory tasks.

Main Methods:

• Utilized mGRASP, a technique reconstituting fluorescent GFP across synaptic clefts.
• Identified engram neurons using IEGs: Arc and cFos.
• Employed transgenic ArcCre^ERT2 and viral cFostTA systems for genetic targeting.
• Assessed mGRASP labeling following novel environment exposure and a hippocampal-dependent memory task.

Main Results:

• mGRASP successfully labeled synaptic engrams between hippocampal CA1 and CA3 neurons.
• Transgenic ArcCre^ERT2 mediated more efficient synaptic engram labeling compared to viral cFostTA.
• Differences in labeling efficiency are likely attributable to the genetic systems rather than IEG promoter specificity.

Conclusions:

• mGRASP is a viable tool for visualizing synaptic engrams in the hippocampus.
• The ArcCre^ERT2 genetic system offers superior efficiency for synaptic engram labeling over cFostTA.
• Further research into genetic system variations is warranted for optimizing synaptic engram visualization techniques.