Regional analysis of age-related changes in the cholinergic system of the hippocampal formation and basal forebrain of the rat.

In an attempt to clarify conflicting reports of age-related changes in cholinergic systems of the rat hippocampal formation and basal forebrain, we compared aged (40 months) and adult (12 months) male rats using quantitative, regional receptor autoradiography in addition to radiolabelled assays of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). The activities of ChAT and AChE in Ammon's horn/subiculum are 24% and 38% lower, respectively, in the aged brains. There is also a drop in both ChAT (38%) and AChE (28%) activities in the septum, and a 46% drop in ChAT activity in the nucleus basalis of aged rats. In the septal pole of the hippocampal formation there is no significant change with age in binding of the muscarinic antagonist, tritiated quinuclidinyl benzylate (3H-QNB) in any hippocampal subregion. However, specific binding in the temporal pole is higher in the subiculum (40%), CA (27%), and dentate gyrus (25%) of the aged animals. Because some of the neurons of the diagonal band of Broca project to the temporal areas of the hippocampal formation by way of a ventral pathway, it is possible that with age this septohippocampal pathway is selectively affected. Particularly in Ammon's horn and the subicular regions of the aged rat hippocampus, postsynaptic muscarinic receptors may upregulate to compensate for decreases in presynaptic cholinergic activity.