Early growth response gene 1 (Egr-1) is required for new and reactivated fear memories in the lateral amygdala

Abstract

The immediate-early gene early growth response gene-1 (EGR-1, zif-268) has been extensively studied in synaptic plasticity and memory formation in a variety of memory systems. However, a convincing role for EGR-1 in amygdala-dependent memory consolidation processes has yet to emerge. In the present study, we have examined the role of EGR-1 in the consolidation and reconsolidation of amygdala-dependent auditory Pavlovian fear conditioning. In our first series of experiments, we show that EGR-1 is regulated following auditory fear conditioning in the lateral nucleus of the amygdala (LA). Next, we use antisense oligodeoxynucleotide (ODN) knockdown of EGR-1 in the LA to show that training-induced expression of EGR-1 is required for memory consolidation of auditory fear conditioning; that is, long-term memory (LTM) is significantly impaired while acquisition and short-term memory (STM) are intact. In a second set of experiments, we show that EGR-1 is regulated in the LA by retrieval of an auditory fear memory. We then show that retrieval-induced expression of EGR-1 in the LA is required for memory reconsolidation of auditory fear conditioning; that is, post-retrieval (PR)-LTM is significantly impaired while memory retrieval and PR-STM are intact. Additional experiments show these effects to be restricted to the LA, to be temporally graded, and unlikely to be due to nonspecific toxicity within the LA. Collectively, our findings strongly implicate a role for EGR-1 in both the initial consolidation and in the reconsolidation of auditory fear memories in the LA.

A BDNF sensitive mechanism is involved in the fear memory resulting from the interaction between stress and the retrieval of an established trace

“…Recently, Maddox et al (2011), using an auditory Pavlovian fear protocol, indicated that Zif268 response in LA is required for both new association and reactivation of consolidated fear memories (Maddox et al 2011). The reason for these discrepancies in the amygdala nuclei remains unclear; however, it has been suggested that such controversies depend on the context properties since the amygdala modulates the contextual representation when the context is novel (Davis et al 2003;Ploski et al 2010).…”

The Regulation of Transcription in Memory Consolidation

“…Although the underlying mechanisms are much less understood, it has been found that memory reactivation reinitiates a phase of gene expression, as revealed by the amnesia caused when either mRNA synthesis or the function of transcription factors is inhibited after retrieval (Sangha et al 2003;Suzuki et al 2004;Da Silva et al 2008;Maddox et al 2010;Cheval et al 2012;Arguello et al 2013). As in consolidation, the necessity of mRNA transcription in reconsolidation has been observed in many species ranging from invertebrates like Lymnaea stagnalis to mammals (Sangha et al 2003;Suzuki et al 2004;Merlo et al 2005;Arguello et al 2013;Veyrac et al 2014), indicating its general and evolutionarily conserved role in the fragile phases of memory.…”

Social descent with territory loss causes rapid behavioral, endocrine, and transcriptional changes in the brain

“…Thus, higher egr-1 levels in the Dl of non-descenders could indicate activation of memory retrieval circuits required for the social challenge that was not needed in the control situation. In the mammalian amygdala, egr-1 also plays an important role in learning and memory of contextual fear (Malkani et al, 2004;Maddox et al, 2011). In mice, for example, experimental reduction of egr-1 in the lateral amygdala interferes with contextual fear conditioning (Malkani et al, 2004), and egr-1 is thought to be involved in both the initial consolidation and subsequent reconsolidation of fear memories (Maddox et al, 2011).…”

“…In the mammalian amygdala, egr-1 also plays an important role in learning and memory of contextual fear (Malkani et al, 2004;Maddox et al, 2011). In mice, for example, experimental reduction of egr-1 in the lateral amygdala interferes with contextual fear conditioning (Malkani et al, 2004), and egr-1 is thought to be involved in both the initial consolidation and subsequent reconsolidation of fear memories (Maddox et al, 2011). The Dm is the putative teleost homolog of the ventral pallial components of the mammalian amygdala, and lower egr-1 levels in non-descending males could facilitate reduced fear conditioning during the intruder interaction, thereby ensuring his continued 'boldness' in future male-male contests.…”