Two types of cholinergic neurons

2020. június 22.

The cholinergic neurons of the basal forebrain play important roles in multiple cognitive functions and their selective loss leads to cognitive decline during both pathological conditions, such as Alzheimer’s disease, and normal aging. Despite heterogeneous functions spanning multiple temporal scales, functional classes of cholinergic neurons have not yet been identified. Synchronous versus asynchronous activation of subcortical inputs may have substantially different impact on cortical computations. However, synchrony between individual cholinergic units has not yet been tested.

Cholinergic and GABAergic neurons in the basal forebrain. (Credit: Panna Hegedüs)

To address these questions, we analyzed the activity of basal forebrain cholinergic neurons of mice performing a sound-based learning task. We identified two separate types of cholinergic neurons, one showing regular rhythmic activity, while the other exhibiting irregular activity with fast bursts of action potentials.

By using correlation techniques, we found that the irregular, burst-firing cholinergic neurons showed synchronous activation, while the regular rhythmic neurons rarely synchronized. Accordingly, these types also showed differential influence on cortical neuronal activity and mouse decisions.

Cholinergic neurons in the nucleus basalis of Meynert (credit: Balázs Hangya)

Future studies will show whether the two types of cholinergic neurons uncovered here have different involvement in neurodegenerative diseases. If yes, it will be worth exploring possible steps towards developing drugs that selectively target different types of central cholinergic neurons.

The original paper is available here.