Previous studies show that new sensations are being stored continually in the hippocampus, the brain’s control center of memory. However, at the same time, the hippocampus is also the guardian of memories, in that it retrieves stored information from the memory archives. However, it is still unclear as to how the hippocampus records new information with interference from past memories. An influential hypothesis posits that acetylcholine, which is released in the hippocampus during novel experiences and learning, has an important role in mediating the interplay between encoding and retrieval. The current study shows that acetylcholine stimulates astrocytes which are then induced to release the transmitter glutamate; the released glutamate then activates inhibitory nerve cells which inhibit a pathway mediating the retrieval of memories.
The current study used a combination of optogenetics, in vivo and in vitro patch-clamp, and multiphoton imaging to show that acetylcholine release can cause slow inhibition of principal neuronal activity via astrocyte intermediaries. Results show that acetylcholine release from cholinergic septohippocampal projections causes a long-lasting GABAergic inhibition of hippocampal dentate granule cells. Data findings show that this inhibition is caused by cholinergic activation of hilar astrocytes, which provide glutamatergic excitation of hilar inhibitory interneurons.
The group note that the excitatory action of astrocytic activation is mainly observed in neurons located within the dentate hilus. They observed that excitation of cells with dendrites within the molecular layer, such as semilunar granule cells, molecular layer interneurons, or granule cells was more rarely observed. They conclude that this is consistent with the view that glutamate released from astrocytes can have specific actions on some, but not other neuronal networks within the same region.
The team surmise that there are indications that the controlled secretion of acetylcholine is disrupted in patients with Alzheimer’s dementia. For the future, the researchers state that their findings may also shed new light on the cellular causes of memory disorders.
Source: University of Bonn