Classification, Function, and Location of Cholinergic Neurons
The brain cholinergic system forms an extensive network of projection neurons, which innervate several brain areas. These neurons, defined as cholinergic because they contain the machinery for synthesizing and releasing acetylcholine (ACh) for neurotransmission, are grouped in nuclei. They include:
The forebrain cholinergic neurons, forming a series of nuclei in the medial septum, the diagonal band of Broca, and the basal magnocellular nucleus of Meynert (NBM). They are among the largest and most complex neurons, with an axon length up to 50 cm and more than 1000 branch points. They are usually identified as Ch1, located in the medial septum, Ch2 in the ascending, Ch3 in the horizontal limbs of the diagonal band of Broca, respectively, and Ch4 in the NBM. The cholinergic neurons represent between 50 to 75% of the cells present in these nuclei and their projections form the main cholinergic input to the cerebral cortex, hippocampus, olfactory bulb, and amygdala. The widespread extension of the forebrain cholinergic system has been confirmed by analyzing, by magnetic resonance imaging, the parallel atrophy of the cholinergic neurons and the projecting cortical regions in patients affected by mild cognitive impairment (MCI).
The large, aspiny cholinergic interneurons of the caudate nucleus and putamen.
The cholinergic nuclei of the brainstem include the peduncle-pontine nucleus (PPN) Ch5, the dorsolateral tegmental nucleus (DLN) Ch6, the medial habenular nucleus Ch7, and the parabigeminal nucleus Ch8. Ch5 and Ch6 neurons project to the thalamus, hypothalamus, globus pallidus, forebrain cholinergic nuclei, and striatum, Ch7 neurons project to the interpeduncular nucleus, and Ch8 to the superior colliculus.
Fig.1 Schematic representation of some cholinergic pathways in the postnatal rat brain. (Shabani, 2020)
Cholinergic Neurons and Diseases
Post-mortem studies and in vivo neuroimaging investigations demonstrated that in Alzheimer's disease (AD), a loss of forebrain cholinergic nuclei from Ch1 to Ch4 is associated with cognitive deficits, ranging from MCI to dementia. A similar neuropathological situation characterizes alcoholic and post-traumatic dementia. Conversely, in Parkinson's disease (PD) without dementia, the forebrain cholinergic neurons are spared but there is a substantial loss of midpontine cholinergic neurons (C5 and C6), which contributes to the motor and sleep disturbances of this disease. Between these two conditions, there are Lewy body dementia (LBD), PD with dementia, and the Parkinsonian syndromes in which both forebrain and midpontine cholinergic nuclei are affected with the possible involvement of striatal cholinergic neurons.
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Shabani, Z., et al. An Overview of Nicotinic Cholinergic System Signaling in Neurogenesis. Arch Med Res. 2020, 51(4): 287-296.