Cholinergic suppression of hippocampal sharp-wave ripples impairs working memory

Area of Science:

• Neuroscience
• Cognitive Science

Background:

• Cholinergic transmission and hippocampal theta oscillations are vital for learning and memory.
• The precise role of septo-hippocampal cholinergic signaling across different memory phases remains incompletely understood.

Purpose of the Study:

• To investigate the dynamics of hippocampal acetylcholine signaling during different brain states.
• To determine the impact of medial septal cholinergic neuron stimulation on memory performance and hippocampal activity.

Main Methods:

• Utilized a G protein-coupled receptor-activation-based acetylcholine sensor (GRAB_ACh3.0) with fiber photometry in mice.
• Employed selective optogenetic stimulation of medial septal cholinergic neurons.
• Assessed memory performance using a hippocampus-dependent spontaneous alternation task.

Main Results:

• Hippocampal cholinergic signaling paralleled theta/gamma power during walking and REM sleep but decreased during sharp-wave ripples (SPW-Rs).
• Optogenetic stimulation of medial septal cholinergic neurons impaired memory performance when applied during the delay phase, not the choice arm.
• This stimulation also reduced the occurrence of SPW-Rs.

Conclusions:

• Septo-hippocampal interactions play a dual, task-phase-dependent role in memory maintenance.
• Both theta oscillations and SPW-Rs are critical components modulated by cholinergic signaling for memory performance.