CA1 Engram Cell Dynamics Before and After Learning.

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Systems Neuroscience

Background:

• Understanding memory formation requires investigating neuronal population dynamics.
• Engram cells, identified by immediate early gene (IEG) expression, are proposed as the cellular basis of memory.
• Prior research suggests engram recruitment via excitability and learning-driven coactivity, but dynamics across learning and recall are unclear.

Purpose of the Study:

• To track CA1 engram population dynamics longitudinally before and after fear conditioning.
• To elucidate how intrinsic dynamics, behavioral state, and stimulus-cued reactivation modulate engram activity.
• To investigate the evolution of engram cell correlations during learning and recall.

Main Methods:

• Activity-dependent genetic tagging combined with longitudinal two-photon calcium imaging in CA1.
• Fear conditioning and trace fear conditioning paradigms.
• Computational modeling of CA3-CA1 circuit dynamics.

Main Results:

• Spontaneous activity during rest predicted future engram membership up to two days prior to Fos expression.
• Locomotion recruited both engram and non-engram cells, with engram cells showing less velocity modulation.
• A subset of engram cells exhibited increased correlations after fear learning during quiet rest.
• Conditioned stimulus presentation in trace fear conditioning induced elevated activity and stable correlations in engram cells.
• Computational models supported experimental findings, indicating a role for excitatory-inhibitory balance and CA3-driven reactivation.

Conclusions:

• Engram population dynamics are influenced by spontaneous neural states, behavioral context, and memory processes.
• Intrinsic neuronal dynamics play a role in engram cell allocation.
• Fear conditioning leads to learning-dependent reactivation and altered network correlations within engram populations.