Contextual fear retrieval-induced Fos expression across early development in the rat: An analysis using established nervous system nomenclature ontology

The neural circuits underlying the acquisition, retention and retrieval of contextual fear conditioning have been well characterized in the adult animal. A growing body of work in younger rodents indicates that context-mediated fear expression may vary across development. However, it remains unclear how this expression may be defined across the full range of key developmental ages. Nor is it fully clear whether the structure of the adult context fear network generalizes to earlier ages. In this study, we compared context fear retrieval-induced behavior and neuroanatomically constrained immediate early-gene expression across infant (P19), early and late juvenile (P24 and P35), and adult (P90) male Long-Evans rats. We focused our analysis on neuroanatomically defined subregions and nuclei of the basolateral complex of the amygdala (BLA complex), dorsal and ventral portions of the hippocampus and the subregions of the medial prefrontal cortex as defined by the nomenclature of the Swanson (2004) adult rat brain atlas. Relative to controls and across all ages tested, there were greater numbers of Fos immunoreactive (Fos-ir) neurons in the posterior part of the basolateral amygdalar nuclei (BLAp) following context fear retrieval that correlated statistically with the expression of freezing. However, Fos-ir within regions having known connections with the BLA complex was differentially constrained by developmental age: early juvenile, but not adult rats exhibited an increase of context fear-dependent Fos-ir neurons in prelimbic and infralimbic areas, while adult, but not juvenile rats displayed increases in Fos-ir neurons within the ventral CA1 hippocampus. These results suggest that juvenile and adult rodents may recruit developmentally unique pathways in the acquisition and retrieval of contextual fear. This study extends prior work by providing a broader set of developmental ages and a rigorously defined neuroanatomical ontology within which the contextual fear network can be studied further.