Anatomical evidence for direct projections from the entorhinal area to the entire cortical mantle in the rat

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Abstract
The entorhinal area is the most highly differentiated cortical field of the hippocampal formation from an anatomical point of view, and is best known as the origin of the perforant pathway, a massive association projection to the molecular layer of the dentate gyrus and Ammon's horn. This pathway is important as the first link in the so-called “trisynaptic circuit,” which is thought to form the basic unit of information processing in the hippocampal formation and has been implicated in the elaboration of short-term memory and the more permanent storage of selected events in other parts of the cortical mantle. We have reexamined the efferent projections of the lateral entorhinal area with a sensitive new method that utilizes the anterograde axonal transport of a lectin, Phaseolus vulgaris leukoagglutinin (PHA-L), that is not internalized by fibers of passage, and displays labeled axons with the clarity of Golgi impregnations. The results of 5 experiments with injections confined entirely to the lateral entorhinal area suggest that this area sends fibers to innervate the entire cortical mantle, as well as to a longitudinal zone extending the length of the striatum (nucleus accumbens and medial caudoputamen) and the basolateral complex of the amygdala. In an additional series of experiments, injections of the fluorescent retrograde tracer fast blue that were centered in medial prefrontal, somatosensory, auditory, and motor areas of the cortex invariably labeled many neurons in layer IV of the lateral entorhinal area, as well as in other layers, depending on the site of injection. Finally, the results of double retrograde tracer experiments indicated that the 2 densest projections from the lateral entorhinal area--to the medial prefrontal region and to the dentate gyrus and Ammon's horn--arise from essentially separate populations of neurons. These findings serve to clarify the neural mechanisms underlying the role of the hippocampal formation in learning and memory, as well as in locomotor activity associated with goal-oriented behavior.