Similarity in form and function of the hippocampus in rodents, monkeys, and humans

Abstract

We begin by describing an historical scientific debate in which the fundamental idea that species are related by evolutionary descent was challenged. The challenge was based on supposed neuroanatomical differences between humans and other primates with respect to a structure known then as the hippocampus minor. The debate took place in the early 1860 s, just after the publication of Darwin's famous book. We then recount the difficult road that was traveled to develop an animal model of human memory impairment, a matter that also turned on questions about similarities and differences between humans and other primates. We then describe how the insight that there are multiple memory systems helped to secure the animal model and how the animal model was ultimately used to identify the neuroanatomy of long-term declarative memory (sometimes termed explicit memory). Finally, we describe a challenge to the animal model and to cross-species comparisons by considering the case of the concurrent discrimination task, drawing on findings from humans and monkeys. We suggest that analysis of such cases, based on the understanding that there are multiple memory systems with different properties, has served to emphasize the similarities in memory function across mammalian species.

Fig. 1.

Ventral view of a human brain (Top), ventral view of a monkey brain (Middle), and lateral view of a rat brain (Bottom). The major cortical components of the medial temporal lobe are highlighted [perirhinal cortex (red), parahippocampal/postrhinal (blue), and entorhinal cortex (green)]. The organization and connections of these structures are highly conserved across these species. Brains are not drawn to scale.

Fig. 2.

Schematic view of the connections within the medial temporal lobe memory system. The hippocampus, defined here as the DG, CA3, CA1, and subiculum (S), is anatomically situated to receive highly processed information from widespread neocortical regions through three temporal cortical areas, the entorhinal, perirhinal, and parahippocampal cortices (in the rat, the term postrhinal cortex replaces the term parahippocampal cortex), as well as through other direct projections to the entorhinal cortex from areas outside the temporal lobe. The figure shows a simplified view of the way in which information enters the hippocampus from the superficial layers (II and III) of the entorhinal cortex and then flows in a largely unidirectional feed-forward direction to return (predominantly) ultimately to the deep layers of entorhinal cortex (IV and V). The output and input layers refer to the entire entorhinal cortex and not to its medial or lateral subdivisions.

Fig. 3.

Performance on the concurrent discrimination task. (A) Controls (n = 4) learned the task easily within three sessions and performed well on the sorting task 3–6 d later (gray bar). The black bar shows performance immediately afterward, when participants were asked to verbalize their choices rather than reach for objects. Results are means ± SEM. (B) Patient E.P. gradually learned the object pairs across 18 wk. Five days later, he failed the sorting task (gray bar) but then, immediately afterward, performed well in the standard task format while verbalizing his responses (black bar). Seventeen days later, E.P. again failed the sorting task (gray bar) but performed perfectly when 40 trials were given exactly as in original training (white bar). (C) Patient G.P. learned the object pairs gradually during 14 wk. Like E.P., he failed the sorting task on two different occasions, 5 d after training and again 17 d later. In both instances, he performed well immediately afterward when the original task format was reinstated [verbalizing (black bar), standard task (white bar)]. The dashed line indicates chance performance (50% correct). Reproduced from ref. .