Mechanism Behind 'Knowing but Not Recalling' Uncovered: Fluctuations in Brain Histamine Neurons Influence Memory Access

Overview: We often experience moments where we can recall something immediately at one time but struggle at another. A research group led by Professor Hiroshi Nomura at Nagoya City University Graduate School of Medical Sciences, in collaboration with Hokkaido University and Kumamoto University, revealed that this 'fluctuation in memory access' is influenced by slow activity fluctuations of histamine neurons in the brain. The group monitored histamine neuron activity in mice in real time. The results showed that when cues were presented when histamine activity levels were high, memory-based behaviors were observed approximately 40% more frequently compared to when activity was low. This study provides a new perspective on states where memories cannot be recalled, suggesting that memories are not lost, but become harder to access depending on the brain's state.

Key Research Findings: Histamine neuron activity is not constant during wakefulness; it exhibits slow fluctuations on a tens-of-seconds scale, linked to EEG, pupil size, and facial movements. We discovered that the higher the histamine activity just before cue presentation, the stronger the 'expression of memory.' We developed a system to detect histamine activity in real time and present cues accordingly. Using this, we showed that the frequency of mice's responses reflecting memory expression increased by about 40% when histamine activity was high. We also revealed that histamine neurons 'prime' the amygdala, an area involved in memory, creating a 'prepared state' that makes it easier to trigger memory-associated activity patterns when cues arrive.

Background: Conventionally, memory impairment was often understood as the loss of the memory itself. However, this does not explain why the same memory is available at some times but not others. Memory and cognitive functions also fluctuate over time in aging and dementia. In this study, we focused on histamine neuron activity in the brain's deep regions.

Results: Recording histamine neurons in the hypothalamic tuberomammillary nucleus of mice revealed slow fluctuations over several tens of seconds even during wakefulness.