Conditioned cues associated with aversive stimuli can induce opposite responses by the paraventricular thalamus depending on individuals’ genotype

Appetitive and aversive processes rely on largely overlapping brain systems allowing for flexible adaptation of values to variable contexts and subjective states. The paraventricular thalamus (PVT) has been involved in sign-tracking (ST), a measure of individual sensitivity to the incentive salience of conditioned rewards, and in late retrieval of conditioned response to aversive cues. Male mice from the C57BL/6J (C57) and DBA/2J (DBA) inbred strains, whose genotypes differ for ∼5 million known sequence variants, engage different brain areas in associative learning. In specific protocols mice from the two strains do not show differences in development of ST or incubation of cue-conditioned freezing. c-Fos expression measured in C57 mice following ST testing in extinction or after exposure to the fear-conditioned cue late after training (14 days) showed increased expression within the medial-posterior PVT (mpPVT). Instead, c-Fos expression was inhibited in DBA mice tested for ST but increased in mice of this strain exposed to the fear-conditioned cue, in both cases in the anterior PVT (aPVT). An antero-posterior distribution of specific neuronal populations in the PVT, previously associated with anatomic organization of cortical-subcortical connectivity, was confirmed in C57 but not in DBA mice. Finally, excitotoxic lesion of the pPVT were most effective in preventing ST development by C57 mice while only lesions targeting the aPVT were effective in DBA mice.