Histamine in the basolateral amygdala promotes inhibitory avoidance learning independently of hippocampus

Abstract

Recent discoveries demonstrated that recruitment of alternative brain circuits permits compensation of memory impairments following damage to brain regions specialized in integrating and/or storing specific memories, including both dorsal hippocampus and basolateral amygdala (BLA). Here, we first report that the integrity of the brain histaminergic system is necessary for long-term, but not for short-term memory of step-down inhibitory avoidance (IA). Second, we found that phosphorylation of cyclic adenosine monophosphate (cAMP) responsive-element-binding protein, a crucial mediator in long-term memory formation, correlated anatomically and temporally with histamine-induced memory retrieval, showing the active involvement of histamine function in CA1 and BLA in different phases of memory consolidation. Third, we found that exogenous application of histamine in either hippocampal CA1 or BLA of brain histamine-depleted rats, hence amnesic, restored long-term memory; however, the time frame of memory rescue was different for the two brain structures, short lived (immediately posttraining) for BLA, long lasting (up to 6 h) for the CA1. Moreover, long-term memory was formed immediately after training restoring of histamine transmission only in the BLA. These findings reveal the essential 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, our findings indicate that the histaminergic system comprises parallel, coordinated pathways that provide compensatory plasticity when one brain structure is compromised.histamine | hippocampus | amygdala | lateral ventricle | inhibitory avoidance

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

“…As a-FMHis effect on histamine synthesis persists for about 48 h (22), it is conceivable that rats receiving a-FMHis prior to IA training lacked integrity of the histaminergic system during the consolidation process, whereas those treated 24 h after training, during the retrieval. These findings confirm that histamine depletion impairs the consolidation of IA memory (17) and suggest that it also worsens IA-LTM expression by influences on memory retrieval mechanisms. To further test these hypotheses, we investigated whether intracerebral administration of histamine reversed the amnesic effect of histamine depletion caused by a-FMHis.…”

“…We recently showed that intra-LV infusion of a-FMHis (5 μg/μL) quickly and fully suppressed the release of brain histamine measured by microdialysis, which was restored to control levels after about 48 h (17). Thus, to investigate the role of endogenous histamine in retrieval, we examined the performance of rats infused into the LV with a-FMHis 24 h after the IA training session.…”

“…The histaminergic system modulates memory consolidation in many cognitive tasks from IA to fear conditioning and object recognition (14)(15)(16). We recently showed that rats were able to consolidate an IA memory only when the brain histaminergic system was intact (17). Histamine within the brain is synthesized from histidine by histidine-decarboxylase solely in hypothalamic tuberomamillary nucleus neurons (18), which are organized into functionally distinct circuits (19), display selective control mechanisms (19,20), and impinge on different brain regions, including amygdala, prefrontal cortex, and hippocampus, that are responsible for many forms of learning (21).…”

Major neurotransmitter systems in dorsal hippocampus and basolateral amygdala control social recognition memory

“…Meanwhile, it can be concluded from the present data that the CA1 region of the dorsal hippocampus and the BLA are key participants in the regulation of SRM in rats, and that norepinephrine acting on β-receptors, dopamine acting on D1/D5 receptors, and histamine acting on H2 receptors in these two brain regions play a pivotal role in social recognition measured in a standard social discrimination paradigm. The roles of the catecholamines (14,18,38), and to an extent that of histamine (16,36), appear peculiarly interesting because they probably affect this (3) and other forms of memory (14) by actions in the hippocampus and BLA, mediated by the enhanced synthesis of the nuclear CREB (3,16,38), which is related to protein synthesis, here shown to be necessary for SRM, as previously posited by Kogan et al (3).…”

“…In the case of SRM, Kogan et al (3) showed that, in mice, SRM is dependent upon protein synthesis and cyclic adenosine monophosphate responsive-element-binding protein (CREB) function in the hippocampus. Given the fact that the hippocampus and the basolateral amygdala (BLA) work in close association in the making and the regulation of many types of memory (13)(14)(15)(16)(17), we decided to study the participation of both structures in SRM. Historically, the next step to ascertain a putative brain mechanism in a behavior is to examine the eventual role of known neurotransmitters in those structures within the mechanism (13,15).…”