The perforant path, which consists of the projection from the layer II
neurons of the entorhinal cortex to the outer molecular layer of the
dentate gyrus, is a critical circuit involved in learning and memory f
ormation. Accordingly, disturbances in this circuit may contribute to
age-related cognitive deficits. In a previous study, we demonstrated a
decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescenc
e intensity in the outer molecular layer of aged macaque monkeys. In t
his study, we used the optical fractionator, a stereological method, t
o determine if a loss of layer II neurons occurred in the same animals
in which the N-methyl-D-aspartate receptor subunit 1 alteration was o
bserved. Our results revealed no significant differences in the number
of layer II neurons between juvenile, young adult, and aged macaque m
onkeys. These results suggest that the circuit-specific decrease in N-
methyl-D-aspartate receptor subunit I reported previously occurs in th
e absence of structural compromise of the perforant path, and thus may
be linked to an age-related change in the physiological properties of
this circuit. (C) 1997 Elsevier Science Inc.