Hybrid Offspring of C57BL/6J Mice Exhibit Improved Properties for Neurobehavioral Research

C57BL/6 is the most commonly used mouse strain in neurobehavioral research, serving as a background for multiple transgenic lines. However, C57BL/6 exhibit behavioral and sensorimotor disadvantages that worsen with age. We bred FVB/NJ females and C57BL/6J males to generate first-generation hybrid offspring (FVB/NJ x C57BL/6J)F1. The hybrid mice exhibit reduced anxiety-like behavior, improved learning, and enhanced long-term spatial memory. In contrast to both progenitors, hybrids maintain sensorimotor performance upon aging and exhibit improved long-term memory. The hybrids are larger than C57BL/6J, exhibiting enhanced running behavior on a linear track during freely-moving electrophysiological recordings. Hybrids exhibit typical rate and phase coding of space by CA1 pyramidal cells. Hybrids generated by crossing FVB/NJ females with transgenic males of a C57BL/6 background support optogenetic neuronal control in neocortex and hippocampus. The hybrid mice provide an improved model for neurobehavioral studies combining complex behavior, electrophysiology, and genetic tools readily available in C57BL/6 mice.