Mapping and Deciphering Neural Codes of NMDA Receptor-Dependent Fear Memory Engrams in the Hippocampus
(A) Sixty-sec spike raster of 243 simultaneously recorded CA1 units from a control mouse during the first CS/US pairing. Yellow strips indicate the sliding MDA window. (B) MDA dimensionality-reduction statistical projection method show distinct CA1 ensemble patterns (as ellipsoid clusters) represent the Rest (grey), CS (blue) and US (red) activated states. The boundaries of each ellipsoid reflect the 2σ boundaries with Gaussian distributions in the MDA space. Each dot within an ellipsoid shown the MDA subspaces is a statistical result for the ensemble of the simultaneously recorded units from a single trial. The sliding-window method provides the 20-msec resolution of continuous transient ensemble trajectories (or dynamic traces) in response to the CS or US events. A simple CS and US trace during the trial were shown, respectively. The arrows indicate the moving directions of the ensemble trajectories. (C) A CS-to-US associative trace (left) and a US-to-CS associative trace (right) were elicited by the tone or foot shock, respectively, at the 2nd CS/US pairing in the same control mouse. (D) A simple CS trace (left) and US trace (right) in the mutant mouse at the 1st trial. (E) A robust CS or US trace was produced by tone or foot shock, respectively, during the 2nd CS/US pairing trial in the same knockout animal. (F) The occurrences of US-to-CS associative traces triggered by the CS-paired foot shock in all seven trials from the five control mice (left panel) and five knockout mice (right panel). The blue rectangles indicate that the simple US traces produced by paired foot-shock, whereas the red rectangles indicate the US-to-CS associative traces were elicited by the US presentation. (G) The occurrences of CS-to-US associative traces triggered by the tone in all seven trials from the five control mice (left matrix) and five knockout mice (right matrix). The blue rectangles indicate that the simple CS traces produced by paired CS, whereas the red rectangles indicate the CS-to-US associative traces were elicited by the CS presentation during learning.