Acetylcholine Activity Impacts Memory Formation by Modulating Brain Oscillations
Post by Soumilee Chaudhuri
The takeaway
Acetylcholine pathways extensively innervate the hippocampus - a brain region critical for memory formation. This research shows that acetylcholine plays an important role in modulating oscillatory activity in the hippocampus, which affects memory formation.
What's the science?
Acetylcholine is a neurotransmitter that impacts memory formation through its widespread pathways in the brain. Extensive research has also shown that theta oscillations, a type of slow brain wave in the hippocampus are important for memory formation, and are affected by acetylcholine levels in the brain. However, the exact neurophysiological mechanisms of cholinergic circuits in modulating theta oscillations and in aiding hippocampal memory formation are still unclear. This gap has affected the development of therapeutics for patients with memory-related diseases such as Alzheimer’s Disease (AD) that often involve disruption of cholinergic function. This week in Nature Communications, researchers use scopolamine, an acetylcholine antagonist (i.e., blocks acetylcholine), to study how this impacts theta waves in the hippocampus and memory formation.
How did they do it?
The researchers used intracranial brain recordings as well as pharmacological, behavioral, and molecular biology techniques to investigate the link between cholinergic pathways, hippocampal theta oscillations and memory formation. They administered a single dose of scopolamine (an acetylcholine antagonist) to 12 epilepsy patients in the experimental group and administered saline in the control group. Afterwards, both groups participated in a verbal episodic memory task to assess memory performance. Scopolamine disrupts both fast (4-10Hz) and slow (204Hz) hippocampal theta bands in rodent models, so the researchers hypothesized that it would impair these theta oscillations in humans as well and affect memory formation. The researchers analyzed the brain recordings from these patients, looking specifically at three physiological phenomena key for hippocampal memory formation: oscillatory power, phase reset, and synchrony.
What did they find?
The authors found that administration of scopolamine in the experimental group of patients, significantly impaired their memory. This impairment for each patient was accompanied by a disruption of the slow theta oscillation of the hippocampus during memory encoding. Specifically, scopolamine administration suppressed the original length of the slow theta band and interrupted the resetting of the next theta oscillation cycle, preventing an important step in episodic memory formation in the hippocampus. Across all the subjects, it was noticed that this disruption of the theta oscillation correlated with the memory impairment caused by the scopolamine administration. Additionally, it was found that scopolamine also disrupted the synchrony of the theta oscillations. All these findings suggest that cholinergic pathways are critical for hippocampal memory formation through modulation of the temporal dynamics of slow theta wave oscillations.
What's the impact?
The findings of this study demonstrate that acetylcholine disruption significantly influences the dynamics and power of hippocampal theta oscillations crucial for memory formation. These findings have massive implications for potential therapeutic strategies to restore memory in diseases such as dementia and AD.