CHOLINERGIC AND GABAERGIC NEURONS IN THE NUCLEUS BASALIS REGION OF YOUNG AND AGED RATS

Antibodies directed against choline acetyltransferase and glutamic aci d decarboxylase were used in combination with recently developed stere ological techniques to quantify changes in cholinergic, GABAergic, and total neuron number (Nissl-stain) within adjacent tissue sections thr ough the horizontal limb/nucleus basalis in young (3 months, n = 6) an d 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 immuno stained tissue sections were conducted throughout the entire horizonta l limb/nucleus basalis region. A significant 30% decrease in both chol inergic and total neuron number was detected in the aged animals; GABA ergic neuron number remained unchanged. Total neuron number was signif icantly correlated with both cholinergic (r = 0.94) and glial cell num ber (r = 0.63), but not with GABAergic cell number. Based on neuron co unts within an individual thick tissue section, the cholinergic neuron s comprised only 11-15% of all neurons in the nucleus basalis of young and aged animals. Cholinergic neuron loss accounted for only 20% of t he total age-related neuron loss within the horizontal limb/nucleus ba salis in Fischer-344 male rats. These results indicate that age-relate d cholinergic neuron loss within the basal forebrain is reflected in r eductions in total neuron number; however, GABAergic neurons, many of which project to the cortex, are unaffected by age. The magnitude of t he age-related total neuron loss cannot be entirely accounted for by c holinergic cell loss. Therefore, an unidentified non-cholinergic, non- GABAergic component within the basal forebrain is also lost during agi ng and may contribute to the cognitive deficits previously ascribed to cholinergic dysfunction.