Differences in extinction of conditioned fear in C57BL/6 substrains are unrelated to expression of α-synuclein

C57BL/6 mice are commonly used as background strains for genetically modified mice, and little attention is usually paid to the notification of the specific substrain. However, it is known that C57BL/6NCrI (B6N) and C57BL/6JOIaHsd (B6JOIa) mice differ in the course of extinction of conditioned fear (Stiedl 0, Radulovic J, Lohmann R, Birkenfeld K, Palve M, Kammermeier J, et al. Strain and substrain differences in context- and tone-dependent fear conditioning of inbred mice. Behav Brain Res 1999; 104:1-12), as well as in the expression of a-synuclein (Specht CG, Schoepfer R. Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci 200 1;2:11). We tested for a causal relationship between the two findings by employing B6N (expressing a-synuclein), B6JOIa (not expressing alpha-syn) and the third strain C57BL/6JCrl (B6Jax, expressing alpha-syn). We show that (alpha-syn does not account for differences in extinction in a fear conditioning task, as its expression did not covary with the decrease of freezing on repeated non-reinforced tone and context exposure in the three strains: B6Jax exhibited fastest extinction followed by B6JOIa. In contrast, 136N showed persistent fear over the course of extinction training. The differences in extinction between B6JOIa and 136N were unrelated to sensorimotor processing (pain threshold and basal tone reaction) and innate fear (light-dark test). However, B6Jax displayed less innate fear than B6JOIa and B6N. Our results of marked differences in innate and conditioned fear in three B6 substrains illustrate the necessity of a strict adherence to an exact Mouse strain nomenclature. (C) 2004 Elsevier B.V. All rights reserved.