Cholinergic and gabaergic neurons in the nucleus basalis region of young and aged rats

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Antibodies directed against choline acetyltransferase and glutamic acid decarboxylase were used in combination with recently developed stereological techniques to quantify changes in cholinergic, GABAergic, and total neuron number (Nissl-stain) within adjacent tissue sections through the horizontal limb/nucleus basalis in young (3 months, n = 6) and aged (27 months, n = 6) Fischer-344 male rats. Unbiased estimates of total neuron number within these regions were produced using a three-dimensional optical probe, the optical disector, in combination with a systematic random sampling scheme. Estimates of cell counts in immunostained tissue sections were conducted throughout the entire horizontal limb/nucleus basalis region. A significant 30% decrease in both cholinergic and total neuron number was detected in the aged animals; GABAergic neuron number remained unchanged. Total neuron number was significantly correlated with both cholinergic (r = 0.94) and glial cell number (r = 0.63), but not with GABAergic cell number. Based on neuron counts within an individual thick tissue section, the cholinergic neurons comprised only 11-15% of all neurons in the nucleus basalis of young and aged animals. Cholinergic neuron loss accounted for only 20% of the total age-related neuron loss within the horizontal limb/nucleus basalis in Fischer-344 male rats. These results indicate that age-related cholinergic neuron loss within the basal forebrain is reflected in reductions in total neuron number; however, GABAergic neurons, many of which project to the cortex, are unaffected by age. The magnitude of the age-related total neuron loss cannot be entirely accounted for by cholinergic cell loss. Therefore, an unidentified non-cholinergic, non-GABAergic component within the basal forebrain is also lost during aging and may contribute to the cognitive deficits previously ascribed to cholinergic dysfunction.