Topographical distribution of muscarinic cholinergic receptors in the cerebellar cortex of the mouse, rat, guinea pig, and rabbit: a species comparison.

Light microscopic autoradiography of [3H]quinuclidinyl benzilate (QNB) binding sites was used to study the distribution of muscarinic acetylcholine receptors in the mouse, rat, guinea pig, and rabbit cerebellar cortex. In the mouse, the laminar distribution of grain density was similar throughout the cortex, with slightly higher levels over lobules IX and X. The highest [3H]QNB labeling was present over the granule cell layer, and low levels were observed over the molecular layer. In the rat, the general distribution was similar to that of the mouse in that the granule cell layer was most densely labeled and the highest concentration of [3H]QNB binding sites was present in lobules IX and X of the archicerebellum. In these lobules, however, the laminar distribution of grain density was reversed so that the molecular layer was more densely labeled than the granule cell layer. In addition, several discrete columns of elevated grain density traversed the granule cell layer in caudal regions of lobule IX. The distribution of [3H]QNB binding sites in the guinea pig cerebellum was similar to that of the rat in that the molecular layer of lobules IX and X was again more intensely labeled than other cerebellar regions. In the remaining lobules, grain density was equal over the granule cell and molecular layers. In the rabbit cerebellar cortex, slightly higher grain density was observed in the granule cell layer than in the molecular layer. In lobules IX and X and in the hemisphere of X, the Purkinje cell layer was most densely labeled; parasagittal columns of very high grain density were present over the molecular layer of several cortical regions, including lobules I, II, III, IV, V, IX, X, and the hemispheres of IX and X. Since muscarinic receptors have previously been found on blood vessels, there is a possibility that some proportion of receptor labeling may be localized to these structures. Microvessels and capillaries in each of the species examined were more numerous in the granule cell layer than in the molecular layer and white matter. The distribution of blood vessels in many cerebellar lobules of mice, rats, and guinea pigs corresponded quite closely to the general distribution of [3H]QNB binding sites. Unique patterns of labeling in lobules IX and X were not accompanied by corresponding patterns of blood vessel distribution, however. In the mouse, there was a slight increase in muscarinic receptor density observed in the archicerebellum, with no corresponding increase in the density of blood vessels. In the rat and guinea pig, the highest receptor densities in the archicerebellum were observed in the molecular layer rather than in the granule cell layer, a reversal of the laminar pattern in the remaining lobules. There was no corresponding reversal in laminar microvessel density in this region. In addition, columnar patterns of elevated grain density, observed in the cerebellar vermis of rats, guinea pigs, and rabbits, were not accompanied by corresponding patterns of increased microvessel density. It is concluded that, although some proportion of paleo- and neocerebellar muscarinic receptors may be localized to microvessels and capillaries, the unique patterns of [3H]QNB binding sites in the archicerebella of all four species, plus the discrete columns of high grain density observed in the rat, guinea pig, and rabbit, may reflect the presence of neuronal receptors.