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The trisynaptic pathway from entorhinal cortex to the hippocampus has long been regarded as the major route of information transfer underlying memory consolidation. Most physiological studies of this pathway involve recording from hippocampal slices. We have used both single- and double-label 2-deoxyglucose autoradiographic methods to image the pattern of activation in the hippocampal formation of 14 rhesus monkeys performing cognitive tasks, varying in content (spatial or nonspatial), process (working memory or associative memory), and mode of response (oculomotor or manual). These studies revealed a highly differentiated pattern of metabolic activation throughout the rostrocaudal extent of the hippocampal formation that was common to all behavioral conditions examined. This pattern consisted of intense activation of the stratum lacunosum-moleculare of CA1 and the subiculum, contrasting with barely detectable activity in CA3 and modest activation in the dentate gyrus, which did not include its molecular layer. These findings indicate a remarkable invariance in hippocampal activation under conditions of varied content, varied process, and varied mode of response and an heretofore-unappreciated preferential engagement of the direct rather than the trisynaptic pathway during performance of a wide range of behavioral tasks.

Prominence of Direct Entorhinal–CA1 Pathway Activation in Sensorimotor and Cognitive Tasks Revealed by 2-DG Functional Mapping in Nonhuman Primate