Threat intensity shapes cortical engram architecture supporting remote memory retrieval

Area of Science:

• Neuroscience
• Memory Research
• Cellular Biology

Background:

• The strength and persistence of threat memories are influenced by the intensity of the initial aversive experience.
• Understanding the neural mechanisms underlying memory strength is crucial for addressing conditions like PTSD.

Purpose of the Study:

• To investigate how threat intensity during contextual threat conditioning (CTC) affects the physiological and structural properties of prelimbic cortex (PL) pyramidal neurons.
• To identify the role of PL engram cells in the retrieval of threat memories of varying intensities.

Main Methods:

• Utilized engram tagging, chemogenetics, and electrophysiology in male mice.
• Performed spine analyses to examine structural changes in neuronal dendrites.
• Compared neuroadaptations following mild versus strong CTC.

Main Results:

• PL engram cells selectively mediate the retrieval of mild remote threat memories.
• Neuroadaptations in PL engram cells are time-dependent, dendritic segment-specific, and modulated by threat intensity.
• Increased presynaptic release probability and reduced postsynaptic strength occurred regardless of threat intensity, while long thin spine addition was specific to mild CTC on oblique dendrites.

Conclusions:

• Threat intensity critically shapes the cortical engram architecture underlying memory representation.
• Specific structural changes, like spine addition on oblique dendrites, are associated with mild threat memory retrieval.
• These findings provide insights into the neural basis of threat memory strength and persistence.