For years, researchers have been working to discover which cellular processes allow humans to learn and store memories, and how these processes are compromised by diseases such as schizophrenia and Alzheimer’s. Researchers at NIH say they believe they have uncovered one piece to this puzzle.

Neurons in the brain communicate with one another through the use of neurotransmitters — chemicals which stimulate electrical signals in neighboring neurons. Studies in mice have shown that the timing of when the neurotransmitter acetylcholine is released into the hippocampus may play a key role in regulating synaptic strength.

Researchers Jerrel Yakel, PhD, and Zhenglin Gu, PhD — investigators in the National Institute of Environmental Health Sciences (NIEHS) — developed a study group of mice whose neurons produced a light-sensitive protein. They were then able to use a laser to stimulate these neurons to release acetylcholine.

They were able to demonstrate that, when the neurons were stimulated to release acetylcholine at just the right time in the hippocampus, they could induce a cellular change in synapses that use glutamate. Glutamate, another neurotransmitter, has been found to be key in learning and memory and in long-term potentiation — a long-lasting enhancement in signal transmission between neurons.

The NIEHS research team found that timing was crucial and that even a few hundredths of a second in the timing of the acetylcholine release could affect how adjacent neurons responded. A difference as small as 20 milliseconds in the timing of the laser could result in very different reactions.

According to Yakel, these findings might represent a first step in studying disorders that affect learning and memory, such as schizophrenia and Alzheimer’s. People with Alzheimer’s have been shown to have low levels of acetylcholine in the cerebral cortex. A similar deficit has been shown among patients with schizophrenia, with acetylcholine depletion being linked to visual hallucination in schizophrenic patients.

1: Gu Z, Yakel JL. Timing-dependent septal cholinergic induction of dynamic hippocampal synaptic plasticity.Neuron. 2011 Jul 14;71(1):155-65. PubMed PMID: 21745645; PubMed Central PMCID: PMC3134790.