Differential expression of the immediate early genes c-Fos, Arc, Egr-1, and Npas4 during long-term memory formation in the context preexposure facilitation effect (CPFE)

Abstract

The context preexposure facilitation effect (CPFE) is a contextual fear conditioning paradigm in which learning about the context, acquiring the context-shock association, and retrieving/expressing contextual fear are temporally dissociated into three distinct phases (context preexposure, immediate-shock training, and retention). The current study examined changes in the expression of plasticity-associated immediate early genes (IEGs) during context and contextual fear memory formation on the preexposure and training days of the CPFE, respectively. Using adolescent Long-Evans rats, preexposure and training day expression of the IEGs c-Fos, Arc, Egr-1, and Npas4 in the medial prefrontal cortex (mPFC), dorsal hippocampus (dHPC), and basolateral amygdala (BLA) was analyzed using qPCR as an extension of previous studies from our lab examining Egr-1 via in situ hybridization (Asok, Schreiber, Jablonski, Rosen, & Stanton, 2013; Schreiber, Asok, Jablonski, Rosen, & Stanton, 2014). In Expt. 1, context preexposure induced expression of c-Fos, Arc, Egr-1 and Npas4 significantly above that of home-cage (HC) controls in all three regions. In Expt. 2, immediate-shock was followed by a post-shock freezing test, resulting in increased mPFC c-Fos expression in a group preexposed to the training context but not a control group preexposed to an alternate context, indicating expression related to associative learning. This was not seen with other IEGs in mPFC or with any IEG in dHPC or BLA. Finally, when the post-shock freezing test was omitted in Expt. 3, training-related increases were observed in prefrontal c-Fos, Arc, Egr-1, and Npas4, hippocampal c-Fos, and amygdalar Egr-1 expression. These results indicate that context exposure in a post-shock freezing test re-engages IEG expression that may obscure associatively-induced expression during contextual fear conditioning. Additionally, these studies suggest a key role for long-term synaptic plasticity in the mPFC in supporting the CPFE.

Role of prelimbic cortex PKC and PKMζ in fear memory reconsolidation and persistence following reactivation

“…Moreover, it was reported that ZIP infused into the insular cortex impaired the taste aversion memory persistence 1 month after its infusion 36 . We investigated the PL cortex ZIP effects on memory persistence by using a protocol of contextual fear conditioning with a familiarization session, in which the contribution of the medial prefrontal cortex to long-term memory is greater than in protocols without pre-exposure to the context to-be-conditioned 41 , as used in those works 23,36 . Thus, differences in protocols and the brain areas where ZIP was infused may account for the mixed findings observed.…”

Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes

“…FOS and JUN are responsive to adrenergic stimulation in rat cardiomyocytes [ 40 ] suggesting a conserved regulatory response to NE between rat and human, in cardiomyocytes and adipocytes. Nevertheless, the bulk of knowledge about IEGs and their regulation is based on studies of neurons and the nervous system [ 80 – 82 ]. In those models, the main functions described are proliferation, differentiation, survival [ 83 ], and stem cells fate [ 84 ].…”

Neonatal ethanol exposure impairs long-term context memory formation and prefrontal immediate early gene expression in adolescent rats

“…Importantly, our lab has recently shown that both the dorsal hippocampus (dHPC) and medial prefrontal cortex (mPFC) are required during all three phases of the CPFE [43][44][45]. Additionally, context preexposure and immediate-shock training induces the expression of the activityand plasticity-associated immediate early genes (IEGs) c-Fos, Arc, Npas4, and Egr-1 in the mPFC and dHPC [46,47]. These combined neural and behavioral aspects of the CPFE may explain why it is more sensitive to neonatal alcohol exposure than traditional "hippocampusdependent" behavioral tasks such as single-trial standard contextual fear conditioning (sCFC) or maze-learning tasks commonly used in FASD models [24,36].…”