Optical and computational dissection of emergent prefrontal rewiring to encode fear memory

The prefrontal cortex regulates various emotional behaviors and memories, and prefrontal dysfunction can trigger psychiatric disorders. While untangling the internal network may provide clues to the neural architecture underlying such disorders, it is technically difficult due to the complexity and heterogeneity of the network. Here we propose an optical and computational dissection of the internal prefrontal network utilizing chronic two-photon imaging and a sparse modeling algorithm, which enabled the discrimination of newly emerged neuronal ensembles specifically encoding conditioned fear responses. Further graphical modeling revealed that neurons responding to the unconditioned stimulus during fear conditioning became a core of the ensembles with an enhanced capability for pattern completion, demonstrating activity-dependent rewiring upon the associative learning.Using chronic two-photon imaging and sparse modeling, we successfully discriminated neural ensembles encoding conditioned responses (CR ensembles).We confirmed that the CR ensembles were distinct from neurons encoding regular locomotion and emerged as a result of fear conditioning.Enhanced coactivity and functional connectivity were specifically observed in CR ensembles as a result of fear conditioning.Further graphical modeling revealed the signature of the construction of the conditioned stimulus-unconditioned stimulus (US) association circuit by rewiring around the US responsive pattern completion cells in an experience-dependent manner.