Muscarinic receptor changes in the gerbil thalamus during aging

Here we studied muscarinic receptors in the gerbil thalamus at 8 different ages — from 6 to 36 months — using receptor and functional autoradiography. The pharmacological profile inhibiting [3H]N-methyl scopolamine ([3H]NMS) binding with 50 and 200 nM pirenzepine, 30 nM pFHHSiD and 100 nM AF-DX 116 revealed the predominance of the M2 muscarinic subtype in the thalamic nuclei studied, mainly in the anteroventral, anteromedial and paraventricular thalamic nuclei. These data correlated with the highest [35S]guanylyl-5′-O-(γ-thio)-triphosphate ([35S]GTPγS) binding induced in these nuclei by the muscarinic agonist oxotremorine in functional autoradiographic assays. Significant aging-dependent increases in the functional response in these three nuclei were observed, but only the anteroventral and anteromedial thalamic nuclei showed aging-dependent increases in [3H]NMS binding. Since these nuclei exert relevant functions, in which cholinergic pathways are involved and acetylcholine release is reported to decrease during aging, we suggest that the anteroventral and anteromedial thalamic nuclei would play critical roles in the cholinergic transmission that require compensatory mechanisms during the aging process and that are not observed in other thalamic nuclei.