Auditory conditioned fear elicits anxiety-like behavior and differential neuronal remodeling in the prelimbic and infralimbic cortex of rats.

Fear and anxiety are adaptive responses that promote survival. Defensive immobility, including tonic and dorsal forms, is a multisensory behavior. However, the relationship between learned fear and immobility, as well as underlying cortical adaptations, remains unclear. Here, we induced an auditory conditioned fear in adult rats and assessed its effects on locomotion, light/dark preference, and two immobility paradigms, alongside neuroarchitectural changes in the medial prefrontal cortex including the prelimbic (PrL) and infralimbic (IL) cortices. Conditioned rats spent significantly less time in the light compartment and more time in the dark compartment of the light/dark box. In the open-field test, they exhibited reduced distance traveled and increased freezing behavior. Dorsal immobility duration was elevated in conditioned rats, whereas neck-clamp immobility remained unaffected. Morphological analyses revealed region-specific alterations in prefrontal cortical structure: conditioned rats displayed hypertrophy in the PrL cortex, while the IL cortex showed hypotrophy and reduced spine density. These opposing, region-dependent changes suggest differential cortical adaptations associated with learned fear. Together, these results indicate that conditioned rats display behavioral alterations associated with anxiety-related behavior accompanied by selective neuroarchitectural remodeling within prefrontal circuits implicated in fear regulation. Our findings provide novel insights into the interplay between conditioned fear, defensive immobility, and cortical plasticity, highlighting distinct roles of PrL and IL subregions in modulating adaptive and maladaptive responses to threat.