C-fos expression and accelerated visual cued fear conditioning in mice with visual input directed to the auditory thalamus

Abstract

Neonatal surgery induces retinal axons to innervate the medial geniculate nucleus (MGN) of the thalamus, providing visual input to cells in auditory thalamus and cortex. However, the behavioral consequences of this “rewiring” are largely unknown. In normal mice, a few tone-shock pairings are sufficient to elicit fear to the tone presented alone, whereas a visual cue is less effective: many more light-shock pairings are needed to elicit fear to the light alone. The present study explores whether visual inputs routed to the MGN influence fear conditioning behavior. Bilateral ablation of the inferior colliculus in p0 mice induced retinal innervation of the MGN. As adults, the mice underwent 3 sessions of fear conditioning and behavioral testing. A conditioning session consisted of 10 minutes of habituation followed by 3 cue-shock pairings (30 sec ISI). The cue (auditory or visual) was presented for 5 seconds, co-terminating with a foot shock (2 sec, 0.3 mA). Freezing was subsequently measured in either the conditioning chamber (contextual fear, 24 h) or an altered context chamber (cued fear, 48 h). Thirty minutes after the last testing session, the mice were perfused and immunohistochemistry performed to examine cFOS expression (c-fos is an immediate early gene and its expression correlates with neuronal activity). After only 1 session of fear conditioning rewired, but not sham-lesion, mice froze more during the light presentation than the cued fear testing habituation period. Most sham lesion mice required several sessions to produce this effect. Contextual fear was comparable for all groups. Consistent with the behavior results, after 1 session of fear conditioning c-fos expression was higher in the lateral amygdala for light conditioned rewired mice than for sham lesion mice. Our results indicate that retinal projections directed to the MGN accelerate visual cued fear conditioning and that this pathway conveys novel information capable of mediating behavior.