Central cholinergic system

The central cholinergic system is a vital neurotransmitter network in the brain that employs acetylcholine (ACh) to regulate a wide array of cognitive and physiological functions (PMC6164334). It is primarily composed of cholinergic neurons in the basal forebrain and brainstem that project to the cortex, hippocampus, and thalamus, as well as local interneurons in the striatum (PMC3543019). This system is fundamental to processes such as memory formation, attention, learning, and the maintenance of the sleep-wake cycle. Pathologically, a decline in central cholinergic activity is a defining feature of Alzheimer's disease and other dementias, where the loss of cholinergic neurons correlates with cognitive impairment (PubMed: 12719193). Drugs targeting this system, such as acetylcholinesterase inhibitors like donepezil, aim to increase synaptic ACh levels to alleviate symptoms of cognitive decline (MDPI: 2076-3921/11/11/2145). Additionally, muscarinic and nicotinic receptors within this system are targets for both agonists to enhance cognition and antagonists to treat conditions like Parkinsonian tremors or motion sickness. However, modulating this system requires careful balance, as excessive activity can lead to a cholinergic crisis, while insufficient activity or blockade can cause significant cognitive and autonomic side effects.

Other names

Central cholinergic activityBrain cholinergic systemCholinergic neurotransmissionCentral cholinergic tone

Potentiation or inhibition of cholinergic signaling via acetylcholinesterase inhibition, or direct agonism/antagonism of muscarinic and nicotinic acetylcholine receptors.