Hippocampal NMDA receptor blockade impairs CREB phosphorylation in amygdala after contextual fear conditioning

Abstract

In contextual fear conditioning (CFC), hippocampus is thought to process environmental stimuli into a configural representation of the context and send it to amygdala nuclei, which current evidences point to be the site of CS-US association and fear memory storage. If it is true, hippocampus should influence learning-induced plasticity in the amygdala nuclei after CFC acquisition. To test this, we infused wistar rats with saline or AP5, a NMDA receptor antagonist, in the dorsal hippocampus just before a CFC session, in which they were conditioned to a single shock, exposed to the context with no shocks or received an immediate shock. The rats were perfused, their brains harvested and immunohistochemically stained for cAMP element binding protein (CREB) phosphorylation ratio (pCREB/CREB) in lateral (LA), basal (B) and central (CeA) amygdala nuclei. CFC showed a learning-specific increase in pCREB ratio in B and CeA, in conditioned-saline rats compared to context and immediate shocked ones. Further, conditioned rats that received AP5 showed a decrease in pCREB ratio in LA, B and CeA. Our results support the current ideas that the role of hippocampus in contextual fear conditioning occurs by sending contextual information to amygdala to serve as conditioned stimulus.

Dorsal hippocampal NMDA receptor blockade impairs extinction of naloxone‐precipitated conditioned place aversion in acute morphine‐treated rats by suppressing ERK and CREB phosphorylation in the basolateral amygdala

“…There is considerable evidence that the amygdala and hippocampus are anatomically connected to each other (Pitkanen et al ., ) and functionally interact during encoding of emotional memory (Richardson et al ., ; Calandreau et al ., ). It has been shown that intra‐DH infusion of muscarinic antagonists or NMDA receptor antagonists diminishes contextual fear conditioning‐induced phosphorylation of ERK1/2 or CREB in the BLA (Calandreau et al ., ; de Oliveira Coelho et al ., ). It has also been shown that a lesion in the DH disrupts the context specificity of extinction and impairs the context dependence of amygdala neuronal activity evoked by an extinguished conditioned stimulus (Ji and Maren, ).…”

Differential activation of amygdala Arc expression by positive and negatively valenced emotional learning conditions

“…Molecular markers and immediate-early gene expression induced by new types of learning conditions reflect similar asymmetric patterns of activation. For example, elevated levels of protein kinase C (PKC) or cyclic AMP response element binding protein (CREB) are integral components of the molecular cascades that convert new information from short, to long term memory (Zhou et al, 2009; de Oliveira Coelho et al, 2013; Pinho et al, 2013). Surprisingly both proteins are upregulated in the right, but not left amygdala after exposure to a tone previously paired with an aversive experience such as footshock during fear conditioning training or in response to exposure to a threatening predator (Blundell and Adamec, 2007; Orman and Stewart, 2007).…”

Prefrontal neuronal circuits of contextual fear conditioning

“…Indeed, the HPC and amygdala are functionally connected as measured by local field potentials (LFPs) and within these regions neuroplasticity mechanisms are engaged during both contextual fear conditioning and expression (De Oliveira Coelho et al ; Huff & Rudy ; Lesting et al ; Maren & Hobin ; Trifilieff et al ). Although the roles of the BLA, CeA and dHPC have been well‐documented in contextual fear behavior, they are likely part of a larger neural circuit supporting contextual fear conditioning, as other structures are also necessary for the acquisition and expression of conditioned freezing.…”