br Retrieval requires histamine H receptors in dorsal hippoc

Retrieval requires histamine H1 receptors in dorsal hippocampus Retrieval is a dynamic process that requires neurotransmitter regulation (Barros et al., 2000, Barros et al., 2001). Recently, histamine, and histaminergic transmission has entered the list of putative neurotransmitter modulators of memory retrieval (Myskiw et al., 2016). Fabbri et al. (2016) showed that the integrity of the NSC 66811 mg histaminergic system is necessary for retrieval of inhibitory avoidance memory, because rats depleted of histamine through injections in the lateral ventricles of α-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, displayed impaired inhibitory avoidance memory when tested 48h after training. The inhibitor was administered 24h after training, when the avoidance memory trace was already formed. Infusion of histamine in the hippocampal CA1 region of brain histamine-depleted rats (hence, amnesic) 10min before the retention test restored inhibitory avoidance memory, but was ineffective when given in the basolateral amygdala or the ventral medial prefrontal cortex. Intra-CA1 injections of selective H1 or H2 receptor agonists showed that histamine exerted its retrieval-restoring effect by activating hippocampal H1 receptors (Table 1). The H1 receptor antagonist pyrilamine disrupted avoidance retrieval in rats, which strongly supports an active involvement of endogenous histamine; 90min after the retention test, c-Fos-positive neurons were significantly fewer in the CA1 of the amnestic α-fluoromethylhistidine-treated rats. In these animals, pCREB levels in CA1 were lower than in controls. Increases in pCREB levels are associated with retrieval of associated memories. Targeting the histaminergic system may modify the retrieval of emotional memory; hence, histaminergic ligands might reduce dysfunctional aversive memories and improve the efficacy of exposure psychotherapies. A switch probably at the level of the tuberomamillary nucleus has been suggested to play a role in determining whether H1-mediated stimulant or H2-mediated inhibitory effects should predominate in any given situation (Myskiw et al., 2016). So far, this has been studied in the one-trial step-down inhibitory avoidance task in rats. The “choice” of whether one or other receptor will be activated depends on the recent history of the conditioned stimulus. If the reinforcement had been present in the most recent training trial(s), as following the acquisition of fear tasks (Benetti and Izquierdo, 2013, Da Silva et al., 2006), post-training histamine administration into the dorsal hippocampus facilitates retrieval by an influence on H1 receptors in dorsal hippocampus. If the reinforcement was absent after the last trial or trials, as in extinction training (Bonini et al., 2011), post-training histamine acts instead on H2 receptors and inhibits retrieval, thus promoting and enhancing extinction (see Izquierdo et al., 2016, Myskiw et al., 2016). For additional findings pointing to the feedback role of the lack of reinforcement in determining the future course of the expression of retrieval see Myskiw et al. (2016). Since histamine affects both the consolidation and retrieval of various different tasks, both aversive and non-aversive, it is very likely that its action is exerted upon central mechanisms of consolidation and retrieval processes common to many tasks, rather than on the performance of the corresponding learned response(s) (freezing, performance or inhibition of the performance, sniffing). The dorsal hippocampus has many input and output connections (Izquierdo et al., 2016) involving other temporal lobe structures, the hypothalamus, the central gray, the prefrontal cortex, other regions of the cortex, etc. Some of these connections are linked to response mechanisms (central gray, hypothalamus), but many others are not (basolateral amygdala, entorhinal cortex), and are instead linked to areas that handle the making and the retrieval of various forms of learning and memory (Izquierdo et al., 2006, Izquierdo et al., 2016, Whitlock et al., 2006).