Strain-dependent different role of the Paraventricular Nucleus of the Thalamus in conditioned aversive motivated behavior

Learning associations between stimuli and potentially harmful outcomes is crucial for survival. Such learning relies on cortico-limbic network, with the paraventricular nucleus of the thalamus (PVT) playing a key role in both the retrieval of learned association and the maintenance of long-term fear memories. PVT exhibits distinct anatomo-functional organization along its antero-posterior axis, with different projection systems between its anterior and posterior subregions (respectively aPVT and pPVT). Moreover, recent findings have revealed that these mechanisms operate differently in two inbred strains of C57BL/6J (C57) and DBA/2J (DBA) mice. Thus, the present study aims to highlight strain-dependent differences in the PVT activation during fear recall. C57 and DBA mice were tested for recall of fear 24 hours or 14 days after fear conditioning training. Subsequently, c-Fos expression was quantified in the antero-posterior axis of PVT of both strains (exp.1). Finally, mice received selective infusion of the NMDA agonist N-methyl-D-aspartate (NMDA) into the aPVT and pPVT, and freezing responses were recorded during a fear conditioning test 14 days after training. (exp.2) Our results revealed similar incubation of fear in both strains, but opposite c-Fos expression in response to the threat-associated stimulus. Particularly, DBA mice showed increased c-Fos expression, while C57 mice exhibited decreased expression (exp.1). Finally, only posterior NMDA lesion in DBA mice significantly reduce freezing response (exp.2). Knowledge of the different neural mechanisms underlying similar behaviors responds to the call for searching the link between individual differences and different trajectories to psychopathology, according to the Precision Psychiatry approach.