Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories.

BACKGROUND: A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H3 receptor inverse agonists upregulate histamine release, the inverse agonists may enhance learning and memory. However, whether the inverse agonists promote the retrieval of forgotten long-term memory has not yet been determined. METHODS: Here, we employed multidisciplinary methods, including mouse behavior, calcium imaging, and chemogenetic manipulation, to examine whether and how the histamine H3 receptor inverse agonists, thioperamide and betahistine, promote the retrieval of a forgotten long-term object memory in mice. In addition, we conducted a randomized double-blind, placebo-controlled crossover trial in healthy adult participants to investigate whether betahistine treatment promotes memory retrieval in humans. RESULTS: The treatment of H3 receptor inverse agonists induced the recall of forgotten memories even 1 week and 1 month after training in mice. The memory recovery was mediated by the disinhibition of histamine release in the perirhinal cortex, which activated the histamine H2 receptor. Histamine depolarized perirhinal cortex neurons, enhanced their spontaneous activity, and facilitated the reactivation of behaviorally activated neuronal ensembles. A human clinical trial revealed that treatment of H3 receptor inverse agonists is specifically more effective for items that are more difficult to remember and subjects with poorer performance. CONCLUSIONS: These results highlight a novel interaction between the central histamine signaling and memory engrams.

Functional relevance of the precuneus in verbal politeness.

Non-competitive and non-threatening aspects of social hierarchy, such as politeness, are universal among human cultures, and might have evolved from ritualized submission in primates; however, these behaviors have rarely been studied. Honorific language is a type of polite linguistic communication that plays an important role in human social interactions ranging from everyday conversation to international diplomacy. Here, functional magnetic resonance imaging (fMRI) revealed selective precuneus activation during a verbal politeness judgment task, but not other linguistic-judgment or social-status recognition tasks. The magnitude of the activation was correlated with the task performance. Functional suppression of the activation using cathodal transcranial direct-current stimulation reduced performance in the politeness task. These results suggest that the precuneus is an essential hub of the verbal politeness judgment.

The anodal tDCS over the left posterior parietal cortex enhances attention toward a focus word in a sentence.

The posterior parietal cortex (PPC) has two attentional functions: top-down attentional control and stimulus-driven attentional processing. Using the focused version of the reading span test (RST), in which the target word to be remembered is the critical word for comprehending a sentence (focused word) or a non-focused word, we examined the effect of tDCS on resolution of distractor interference by the focused word in the non-focus condition (top-down attentional control) and on augmented/shrunk attentional capture by the focused word in both the focus and non-focus conditions (stimulus-driven attentional processing). Participants were divided into two groups: anodal tDCS (atDCS) and cathodal tDCS (ctDCS). Online stimulation was given while participants performed the RST. A post-hoc recognition task was also administered in which three kinds of words were presented: target words in the RST, distractor words in the RST, and novel words. atDCS augmented the effect of the focused word by increasing differences in performance between the focus and non-focus conditions. Such an effect was not observed in the ctDCS group. As for the recognition task, atDCS again produced the augmented effect of the focused words in the distractor recognition. On the other hand, ctDCS brought less recognition of non-focused target words in comparison to sham. The results indicate that atDCS promotes stimulus-driven attentional processing, possibly by affecting neural firing in the inferior parietal regions. In contrast, ctDCS appears to prevent retrieval of less important information from episodic memory, which may require top-down attentional processing.