Muscarinic receptors cerebellum

Both nicotinic and muscarinic receptors are widespread in the CNS. Muscarinic receptors with a high affinity for pirenzepine (PZ), M, receptors, predominate in the hippocampus and cerebral cortex, whereas M2 receptors predominate in the cerebellum and brainstem, and M4 receptors are most abundant in the striatum. Central muscarinic and nicotinic receptors are targets of intense pharmacological interest for their potential roles in regulating abnormal neurological signaling in Alzheimer s disease, Parkinson s disease and certain seizure disorders. Nicotinic receptors are largely localized at prejunctional sites and control the release of neurotransmitters [10,11],... 

Increases in cerebral blood flow elicited from stimulation of the basal forebrain are mediated by nicotinic and not muscarinic receptors (Linville et al. 1993). During an attention task, nicotine increases cerebral blood flow to the the anterior cingulate cortex, cerebellum, and occipital cortex, supporting its role in activating attentional systems (Ghatan et al. 1998). 

Fig. 89. Comparison between the distribution of m2 muscarine receptor mRNA (A) and [ H]oxotremorine-M binding to muscarine M2 receptor sites (B) in approximately equivalent coronal sections of rat brain at the level of the caudal cerebellum. Note that m2 mRNAs in the ventral uvula (IX) and the nodulus are localized in the granular layer, whereas M2 receptor binding sites are in the molecular layer (m). 12, hypoglossal nucleus. Scale bar = 3 mm. Vilaro et al. (1992).

Summarizing it appears that the cellular and regional distribution of muscarine receptors in the cerebellum is different between different species. Golgi cells and subpopulations of mossy fibers seem to express muscarine receptors most constantly. An interesting aspect about the presence of muscarine receptors in parallel fibers in rat and rabbit, is that the lobular distribution of m2-containing parallel fibers, is the same as that of ChAT-positive mossy fiber rosettes (see above). This raises the possibility that muscarine m2 receptor are specifically expressed by those granule cells that are innervated by cholinergic mossy fibers. If this proves to be true, this would imply that there... 

Estevez, E.E., JerusaUnsky, D., Medina, J.H., and Robertis, E.D., Cholinergic muscarinic receptors in rat cerebral cortex, basal gangha and cerebellum undergo rapid and reversible changes after acute stress. Neuroscience, 13, 1353, 1984. 

As distinct from the acetyl choline receptor of the neuromuscular junction, the acetyl receptors of the viscera are not blocked by nicotine but are blocked by muscarine. Moreover, based on differences in the binding of the muscarinic antagonist, pirenzapine, the muscarinic acetyl choline receptors (mAChRs), are separated into two classes, viz. high affinity mj receptors, and low affinity m2 receptors. The latter predominates in the heart, cerebellum, and smooth muscle broadly. These different receptors mediate quite different actions. 

Basu N, Stamler CJ, Loua KM, Chan HM. 2005a. An interspecies comparison of mercury inhibition on muscarinic acetylcholine receptor binding in the cerebral cortex and cerebellum. Toxicol Appl Pharmacol 205 71-76. 

A major drawback of many studies of the chemical neuroanatomy is that they were conducted in only one species, the rat. There is extensive evidence for species differences in the distribution of the synthetizing enzyme of acetylcholine (ChAT), muscarinic cholinergic receptors and acetylcholinesterase (see Section 3.10.), and there is reason to assume that a similar interspecies variability exists for other transmitter systems. The expression of Zebrin by certain subpopulations of Purkinje cells, and the zonal patterns in the distribution of 5 -nucleotidase, only occur in certain species. It is a fortunate coincidence for the experimental neuroscientist that the Zebrin zonal pattern is expressed in rats, but in other species like the cat or macaque monkeys all Purkinje cells are Zebrin-immunoreactive. Many species-differences in the chemical neuroanatomy of the cerebellum may be due to the selectivity of the antibodies employed in the im-munocytochemical techniques, but other differences may be real and may reflect true variations in structure or in the transmission and second messenger systems of the cerebellum. 

One of the most active areas of research in molecular imaging is the study of the effect of age. Suhara and colleagues used PET to study the age-related changes in human muscarinic acetylcholine receptors. In persons between the ages of 18 and 75, uptake of [ C]N-methyl piperidyl benzilate continuously increased in all brain areas with the exception of the cerebellum. The binding of the tracer to acetylcholine receptors in eight brain regions (pons, hippocampus, frontal cortex, striatum, temporal cortex, thalamus, occipital cortex, and parietal cortex) showed an age-related decrease of about 45%. 

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