ERK2 and CREB activation in the amygdala when an event is remembered as “Fearful” and not when it is remembered as “Instructive”

Abstract

A training protocol was developed based on durable exposure to the two-way shuttle avoidance task, in which the conditioned stimulus (CS), which was fear evoking for both training conditions on the first day of training, becomes instructive at the end of training under controllable conditions but remains fear evoking under the uncontrollable conditions. The protocol was utilized to examine whether, depending on the training regime, the memory formed will result in a different level of involvement of the amygdala. Three groups of rats were tested: controllable, subjected to durable avoidance learning; uncontrollable, subjected to the same training schedule but with no control over the stressor; and naive. Two weeks later, after the introduction of a reminder cue, freezing response, defecation, and blood corticosterone (CORT) of the uncontrollable group were higher than in the controllable and naive groups, indicating that indeed, for this group, the CS remained fear evoking. Significantly higher than chance shuttling responses of the controllable group indicated that, for them, the CS became "instructive." Activation of ERK2 and CREB in the basolateral amygdala (BLA) was highest in the uncontrollable group compared with the controllable and naive groups. Overall, the results indicate that the training procedure succeeded in dissociating between the physical (electric shock) and the psychological (control) attributes of the experience. Also, our findings support the view that an emotionally charged reminder cue activates the amygdala but that, as a previously fear-evoking memory cue becomes instructive, the involvement of the amygdale lessens.

Differential expression of molecular markers of synaptic plasticity in the hippocampus, prefrontal cortex, and amygdala in response to spatial learning, predator exposure, and stress‐induced amnesia

“…It is also well-established that stress reduces hippocampal expression of brain-derived neurotrophic factor (BDNF), which has been associated with impaired hippocampus-dependent memory (Radecki et al, 2005;Duman and Monteggia, 2006). In contrast, stress or a fear-provoking experience activates molecular plasticity in the amygdala (Pare, 2003;Monfils et al, 2007;Ilin and Richter-Levin, 2009), which exerts an inhibitory influence on hippocampal plasticity (Akirav and Richter-Levin, 1999;Akirav and Richter-Levin, 2006). Therefore, understanding how stress differentially affects molecular plasticity in the hippocampus, amygdala and PFC could enhance our understanding of the complexity of how stress affects learning and memory.…”

Post-Weaning to Pre-Pubertal (‘Juvenile’) Stress: A Model of Induced Predisposition to Stress-Related Disorders

“…Overall, two behavioral profiles of impaired avoidance learning were defined among adult juvenile stressed rats: the first, characterized by low rates of avoidance responses accompanied by high rates of escape-failure responses, was termed ‘Learned helplessness’; the other, characterized by low rates of avoidance and escape-failure responses, termed ‘Bad learners’. Number of escape failures was previously found to be increased also in another model of uncontrollability and depression [30]. …”

“…While most ELS rodent models focus on the perinatal to pre-weaning periods and involve some form of maternal deprivation or separation (for a review, see [25]), we have focused in recent years on an alternative period in the rat ontogeny, ‘juvenility’ (∼28 days), the earlier phase of the adolescent/post-weaning to pre-pubertal period [26,27,30,31,38,44,45,46,49,51,59] (for a summary of the main findings, see tables 1 and 2). …”

CaMKIIα knockdown decreases anxiety in the open field and low serotonin-induced upregulation of GluA1 in the basolateral amygdala

“…Although the precise modality by which GluA1 transcription and translation may be regulated by CaMKII was beyond the focus of the present study, we postulate one common mechanism may be through activation of the cAMP response element-binding protein (CREB) [25]. The CREB transcription factor has been implicated in facilitating states of fear and anxiety [26, 27], and can bind to at least four identified CRE sequences in the GluA1 promoter [27, 28]. As our data suggests, increased CaMKII activation following 5-HT depletion may contribute to hyperexcitability in the BLA, at least in part by subsequently increasing transcription of GluAs.…”