GENOTYPE-DEPENDENT ENGAGEMENT OF ANTERIOR AND POSTERIOR PARAVENTRICULAR NUCLEUS OF THE THALAMUS IN CONDITIONED FEAR INCUBATION

Understanding neural circuits that underly individual variability in psychopathology is critical for the development of personalized therapy. Using two inbred mouse strains, C57BL/6J (C57) and DBA/2J (DBA), we have previously observed similar appetitive and aversive conditioned behaviors despite differences in the recruitment of corticolimbic circuits. Within these circuits, the paraventricular thalamus (PVT) has been described as a “traffic light” for motivated behavior, regulating cue-induced responses based on the salience of the stimulus.
Recent findings indicate that the anterior (aPVT) and posterior (pPVT) subregions function in opposing ways in C57 and DBA mice when exposed to appetitive conditioning. Building on these, the present study aims to investigate the contribution of the aPVT and pPVT to both acquisition and expression of aversive conditioned behaviors, using the fear incubation paradigm, in C57 and DBA mice.
To this aim, mice from both strains received selective lesions (NMDA) in the aPVT or pPVT prior to the fear incubation paradigm (acquisition), or selective inactivation (DREADDs) of these subregions before re-exposure to the cue 14 days after training (expression).
The results confirmed an opposite role for the PVT subregions in C57 and DBA mice, both during acquisition and expression of fear incubation.
Together with previous evidence of divergent PVT involvement during appetitive conditioning, these findings indicate that genetic background shapes PVT functioning when appetitive and aversive behaviors are assessed separately. However, it seems that the PVT is mainly engaged when appetitive and aversive valences occur simultaneously, driving future studies to directly investigate PVT functioning during motivational conflict.