Learning-Dependent Shift from Right to Left CA3 Input Dominance Shapes the Evolution of Right CA1 Spatial Maps

Area of Science:

• Neuroscience
• Cognitive Neuroscience
• Systems Neuroscience

Background:

• CA1 place fields are crucial for spatial memory.
• The precise role of bilateral CA3 inputs in shaping CA1 place fields during learning is not fully understood.

Purpose of the Study:

• To investigate how left and right CA3 projections to the right CA1 (CA1_R) influence the formation and stabilization of spatial maps during novel environment familiarization.
• To elucidate the temporal dynamics of CA3 input dominance in coordinating CA1_R map refinement and stability.

Main Methods:

• Utilized two-photon calcium imaging and optogenetic inhibition in head-fixed mice navigating a virtual track.
• Examined the functional contribution of individual CA3 hemispheres to CA1_R place field development.
• Performed axonal recordings to assess the activity and reliability of CA3 projections.

Main Results:

• CA1_R spatial maps refined over approximately 10 laps, transitioning from an early refinement phase to a late stability phase.
• Right CA3 inputs were dominant during the early phase, driving map refinement and reliable place field formation.
• Left CA3 inputs became dominant in the late phase, contributing to map stability and sustained place field reliability.

Conclusions:

• A shift in CA3 input dominance from right to left occurs during the learning of a novel environment.
• This dynamic shift orchestrates the refinement and subsequent stabilization of CA1_R spatial maps, essential for memory formation.
• The findings provide critical insights into the neural mechanisms underlying hippocampal spatial learning and memory consolidation.