C57BL6 Substrain Differences in Hippocampal-Dependent Learning and Transcriptome

Here, we evaluated B6J and B6NJ substrains in a fear conditioning paradigm with varied conditioned stimulus-unconditioned stimulus pairings to assess if the strength of learning varies between substrains. For all number of pairings, B6NJ showed enhanced contextual freezing compared to B6J. To investigate baseline and learning-induced changes in hippocampal transcriptome that may underlie the observed behavioral differences between B6J and B6NJ, dorsal and ventral hippocampi were analyzed for RNAsequencing from B6J and B6NJ male mice from three groups: direct from home cage, 30 minutes after 2-pairings of shock and cue, 30 minutes after 2 exposures to cue alone. RNASeq pathway and network analysis identified several genes related to BDNF signaling that could contribute to the differences in levels contextual fear learning observed. Together, these behavioral and transcriptomic findings confirm differences in conditioned fear between the commonly used B6 substrains B6J and B6NJ and suggest that hippocampal transcriptome differences related to BDNF may contribute to differences in learning