Exposure to a mildly aversive early life experience leads to prefrontal cortex deficits in the rat

Aversive early life experiences in humans have been shown to result in deficits in the function of the prefrontal cortex (PFC). In an effort to elucidate possible neurobiological mechanisms involved, we investigated in rats, the effects of a mildly aversive early experience on PFC structure and function. The early experience involved exposure of rat pups during postnatal days (PND) 10–13 to a T-maze in which they search for their mother, but upon finding her are prohibited contact with her, thus being denied the expected reward (DER). We found that the DER experience resulted in adulthood in impaired PFC function, as assessed by two PFC-dependent behavioral tests [attention set-shifting task (ASST) and fear extinction]. In the ASST, DER animals showed deficits specifically in the intra-dimensional reversal shifts and a lower activation—as determined by c-Fos immunohistochemistry—of the medial orbital cortex (MO), a PFC subregion involved in this aspect of the task. Furthermore, the DER experience resulted in decreased glutamatergic neuron and dendritic spine density in the MO and infralimbic cortex (IL) in the adult brain. The decreased neuronal density was detected as early as PND12 and was accompanied by increased micro- and astroglia-density in the MO/IL.