AXL1717 Posttraining memory facilitation by histamine

Posttraining memory facilitation by histamine infused into the dorsal hippocampus was also observed in two more recently described and very important non-aversive forms of memory: object recognition (da Silveira, Furini, Benetti, Monteiro, & Izquierdo, 2013) and social recognition (Garrido Zinn et al., 2016). Object recognition seemingly also depends on hippocampal long-term potentiation (Clarke, Cammarota, Gruart, Izquierdo, & Delgado-García, 2010), but in addition it also relies on other mechanisms in the perirhinal AXL1717 (Gervais et al., 2016, Olarte-Sánchez et al., 2015) and other structures of the temporal lobe, including the entorhinal and insular cortex (Balderas, Rodríguez-Ortiz, & Bermúdez-Rattoni, 2015) and the basolateral amygdala (Beldjoud, Barsegyan, & Roozendaal, 2015). The object recognition task, originally described by Ennaceur and Delacour (1988), has become widely used in memory studies in the last few years. In this task, posttraining infusion in the CA1 of the H1-receptor antagonist, pyrilamine, the H2-receptor antagonist, ranitidine, or the H3-receptor agonist, imetit, blocked long-term memory retention in a time dependent manner (30–120min) without affecting general exploratory behavior, anxiety state or hippocampal function. This suggests that in this task the three different histamine receptor types are involved in memory consolidation, which makes it more complex than inhibitory avoidance or even social recognition (da Silveira et al., 2013) (Table 1). In the social recognition task, histamine appears to regulate memory consolidation both in the basolateral amygdala and in the dorsal hippocampus through a variety of neurotransmitter systems, including histamine, acting in both regions through H2 receptors. Posttraining intra-CA1 or intra-basolateral amygdala infusion of the H2 antagonist, ranitidine caused retrograde amnesia for social recognition in rats and the H2 agonist dimaprit reversed this effect. Histaminergic regulation of the consolidation of this behavior seems to operate normally at a high level of endogenous histamine release, since ranitidine has an inhibitory influence on its own, whereas dimaprit on its own has no discernible influence (Garrido Zinn et al., 2016).
Amnesic effect of localized brain histamine synthesis inhibition, and evidence for parallel processing of histamine regulation of consolidation Benetti et al. (2015) found that the integrity of the brain histaminergic system is necessary for long-term, but not for short-term memory of step-down inhibitory avoidance. In addition, they observed that phosphorylation of cyclic adenosine monophosphate responsive-element-binding protein (CREB), a crucial mediator in long-term memory formation (Bernabeu et al., 1997, Josselyn et al., 2004) correlates anatomically and temporally with histamine-induced memory retrieval, showing the active involvement of histamine in the CA1 region of the hippocampus and in the basolateral amygdala in different phases of memory consolidation (Table 1). Additionally, they also reported that the microinfusion of histamine into either hippocampal CA1 or basolateral amygdala of brain histamine-depleted rats, hence amnesic, restored long-term memory. However, the time frame of memory rescue was different for the two brain regions, short lived (immediately post-training) for the basolateral amygdala, long lasting (up to 6h) for the CA1. Moreover, long-term memory was formed immediately after training by restoring histamine transmission only in the basolateral amygdala. These findings reveal the role of histaminergic neurotransmission to provide the brain with the plasticity necessary to ensure memorization of emotionally salient events, through recruitment of alternative circuits. Hence, they fit with other results indicating parallel processing of information in dorsal hippocampus and amygdala in the memory consolidation of inhibitory avoidance (e.g., Izquierdo et al., 1992) and probably other types of learning as well.