Infraslow histaminergic dynamics govern priming states to gate moment-to-moment memory accessibility

Area of Science:

• Neuroscience
• Cellular Biology
• Systems Neuroscience

Background:

• Memory recall is variable, even with identical cues, suggesting brain states influence accessibility.
• The specific cellular and circuit mechanisms behind these state-dependent memory fluctuations are not well understood.

Purpose of the Study:

• To investigate the role of histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) in modulating reward-associative memory expression.
• To elucidate the cellular and circuit principles underlying state-dependent memory fluctuations.

Main Methods:

• Recorded spontaneous activity of histaminergic neurons in the TMN in mice.
• Utilized closed-loop cue delivery synchronized with neural activity.
• Employed optogenetic manipulation of TMN histaminergic neurons and their projections to the basolateral amygdala (BLA).
• Measured cue-evoked BLA population responses.

Main Results:

• TMN histaminergic activity showed infraslow dynamics (0.05-0.1 Hz) correlating with integrated brain-body states.
• Cue delivery during high histaminergic states enhanced memory expression.
• Optogenetic activation/inhibition of TMN histaminergic neurons bidirectionally modulated memory recall.
• Activation of histaminergic terminals in the BLA enhanced memory expression.
• Histaminergic inhibition impaired cue-evoked BLA responses.

Conclusions:

• Ongoing histaminergic activity in the TMN exerts an infraslow, state-setting influence.
• This activity primes BLA circuits for robust cue responses, modulating memory accessibility moment-to-moment.