Memory retrieval of inhibitory avoidance requires histamine H ₁ receptor activation in the hippocampus

Abstract

Retrieval represents a dynamic process that may require neuromodulatory signaling. Here, we report that the integrity of the brain histaminergic system is necessary for retrieval of inhibitory avoidance (IA) memory, because rats depleted of histamine through lateral ventricle injections of α-fluoromethylhistidine (a-FMHis), a suicide inhibitor of histidine decarboxylase, displayed impaired IA memory when tested 2 d after training. a-FMHis was administered 24 h after training, when IA memory trace was already formed. Infusion of histamine in hippocampal CA1 of brain histamine-depleted rats (hence, amnesic) 10 min before the retention test restored IA memory but was ineffective when given in the basolateral amygdala (BLA) or the ventral medial prefrontal cortex (vmPFC). Intra-CA1 injections of selective H 1 and H 2 receptor agonists showed that histamine exerted its effect by activating the H 1 receptor. Noteworthy, the H 1 receptor antagonist pyrilamine disrupted IA memory retrieval in rats, thus strongly supporting an active involvement of endogenous histamine; 90 min after the retention test, c-Fos-positive neurons were significantly fewer in the CA1s of a-FMHis-treated rats that displayed amnesia compared with in the control group. We also found reduced levels of phosphorylated cAMP-responsive element binding protein (pCREB) in the CA1s of a-FMHis-treated animals compared with 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.emory determines the uniqueness of our personal history and is decisive for each individual to survive and prosper. It is a multistate process that includes acquisition, consolidation, and retrieval (1). Whereas considerable advancement has been made toward understanding the specific brain structures (e.g., amygdala, prefrontal cortex, and hippocampus) and molecular mechanisms (receptors and signaling pathways) that underlie acquisition and consolidation (2, 3), the understanding of retrieval has lagged behind, although it is ultimately the only possible measure of memory (4-6). Indeed, retrieval is not simply a static readout of stored information; rather, it represents a dynamic process that can be studied separately from either acquisition or consolidation, with which it shares similar mechanisms (1, 7, 8). Furthermore, retrieval can elicit specific processes that modify the recalled memory (9). In this regard, protein synthesis, a necessary step in the transfer of a labile short-term memory into a stable long-term memory (LTM) (2), is required to enable retrieval, because infusion of protein synthesis inhibitors in the amygdala 10 min before retrieval impaired fear memory expression (10). An interesting question is whether neuromodulatory signaling is required for not only memory acquisition and consolidation (11) but also, retrieval. The...

Carbonic anhydrase activation enhances object recognition memory in mice through phosphorylation of the extracellular signal-regulated kinase in the cortex and the hippocampus

“…Sixty min later, animals were euthanized, the brain dissected on ice and frontal cortices and hippocampi immediately isolated. Western blotting was carried out as described earlier (Fabbri et al, 2016). Briefly, the cortices and the pooled hippocampi (left and right) were individually homogenized in 200 mL ice-cold lysis buffer containing protease and phosphatase inhibitors (50 mM TrisHCl (pH 7.5), 50 mM NaCl, 10 mM EGTA, 5 mM EDTA, 2 mM NaPP, 4 mM PNFF, 1 mM Na 3 VO 4 , 1.1 mM PMSF, 20 mg/mL Leupeptin, 50 mg/mL Aprotinin, 0.1% SDS) and centrifuged at 12,000 rpm at 4 C for 15 min.…”

“…Immediately after sacrifice, the brain was dissected on ice, and the frontal cortex and hippocampi (left and right) isolated. Western blotting was carried out as described earlier (Fabbri et al, 2016). Mice given 2 injections of saline [group 1: saline and saline] served as controls.…”

Neurotransmitters and neuromodulators involved in learning and memory

“…31 Histaminergic system have been shown to influence emotional memory encoding, consolidation, and retrieval. 32 Evidence also point the association of histamine in influencing NMDA induced hippocampal LTP through histamine receptors. 33 Further, histamine also can directly activate NMDA receptor by binding to the polyamine modulatory site.…”

What We Know and What We Need to Know about Aromatic and Cationic Biogenic Amines in the Gastrointestinal Tract

“…In human tissue, HDC is only expressed in a short list of cell types. Among them, several immune differentiated cells (mast cells and basophils) [ 36 , 37 , 38 ], histaminergic neurons [ 18 , 39 ], and gastric enterochromaffin-like cells (ECL cells) [ 40 ] are able to both synthetize and store HIS. Transformed HIS producing cells can preserve or even increase their HIS-producing capacity, as in the case of malignant mastocytosis and several types of gastric cancer cells [ 41 , 42 ].…”

“…Thus, it seems to be a good candidate to participate in gut-brain axis. As HIS and Put, Agm is also a DAO substrate to produce γ-butiramide that is finally converted into γ-guanidinobutirate in CNS [ 39 ]. It can also compete with the other diamines for binding to OCT transporters [ 155 ].…”