Brain histamine is implicated in learning and memory as well as wakefulness, feeding, and neuroendocrine regulation. Previously, we demonstrated histamine H3 receptor inverse agonists upregulate histamine release in the perirhinal cortex and promote the recall of forgotten object memories. However, whether histamine H3 receptor inverse agonists enhance other types of long-term memory and whether activation of histamine neurons is enough for the memory recovery are unclear. First, we tested whether a histamine H3 receptor inverse agonist enhances retrieval of spatial memory on barnes maze task. Thioperamide-treated mice explored a target zone for longer time on a probe test 1 week after training than saline-treated mice. Second, we examined whether chemogenetic activation of histamine neurons in the TMN enhances retrieval of forgotten object memory. We virally targeted hM3Dq, the Gq-coupled excitatory designer receptor exclusively activated by designer drugs (DREADD), to histamine neurons in the TMN of HDC-Cre mice. The mice performed a test session 1 week after training. Pre-test activation of histamine neurons led to a significant increase in the discrimination between novel and familiar objects. These findings indicate that activation of histamine neurons enhances retrieval of forgotten long-term memories.

To: 要旨(抄録)