These data suggest that enhancements in both theta power and the strength of theta-gamma coupling are neural signatures of elevated fear. If so, then coupling during the fear-inducing CS+ should be greater than during the explicitly safe CS− in mice that successfully discriminated between the two stimuli. As expected, we observed enhanced theta-gamma coupling during the CS+ compared to the CS– (Figure S3F; p<.01, sign-rank) in discriminators. The CS− was, however, associated with significantly stronger theta-gamma coupling than the pretone (p<.001, sign-rank), falling between pretone and CS+, likely because freezing to the CS−, though diminished, was still above baseline levels (~20%; Figure S1D). Again, these effects were not entirely explained by theta power differences between CS+, CS−, and pretone (Figure S3F). Notably, the increase in theta-gamma coupling from CS− to CS+ was directly correlated with the increase in freezing from CS− to CS+ on an animal by animal basis (Figure S3G; r=.55, p =.007), substantiating enhanced theta-gamma coupling as a novel neural correlate of enhanced fear.
