This article considers the role of the hippocampus in memory function. A central thesis is that work with rats, monkeys, and humans--which has sometimes seemed to proceed independently in 3 separate literatures--is now largely in agreement about the function of the hippocampus and related structures. A biological perspective is presented, which proposes multiple memory systems with different functions and distinct anatomical organizations. The hippocampus (together with anatomically related structures) is essential for a specific kind of memory, here termed declarative memory (similar terms include explicit and relational). Declarative memory is contrasted with a heterogeneous collection of nondeclarative (implicit) memory abilities that do not require the hippocampus (skills and habits, simple conditioning, and the phenomenon of priming). The hippocampus is needed temporarily to bind together distributed sites in neocortex that together represent a whole memory.

Memory and the hippocampus: A synthesis from findings with rats, monkeys, and humans.

The central theme of the "segregated circuits" hypothesis is that structural convergence and functional integration occurs within, rather than between, each of the identified circuits Admittedly, the anatomical evidence upon which this scheme is based remains incomplete The hypothesis continues to be predicated largely on comparisons of anterograde and retrograde labeling studies carried out in different sets of animals Only in the case of the "motor" circuit has evidence for the continuity of the loop been demonstrated directly in individual subjects; for the other circuits, such continuity is inferred from comparisons of data on different components of each circuit obtained in separate experiments Because of the marked compression of pathways leading from cortex through basal ganglia to thalamus, comparisons of projection topography across experimental subjects may be hazardous Definitive tests of the hypothesis of maintained segregation await additional double- and multiple-label tract-tracing experiments wherein the continuity of one circuit, or the segregation of adjacent circuits, can be examined directly in individual subjects It is worthy of note, however, that the few studies to date that have employed this methodology have generated results consistent with the segregated circuits hypothesis Moreover, single cell recordings in behaving animals have shown striking preservation of functional specificity at the level of individual neurons throughout the "motor" and "oculomotor" circuits It is difficult to imagine how such functional specificity could be maintained in the absence of strict topographic specificity within the sequential projections that comprise these two circuits This is not to say, however, that we expect the internal structure of functional channels (eg, the "arm" channel within the "motor" circuit) to have cable-like, point-to-point topography When the grain of analysis is sufficiently fine, anatomical studies have shown repeatedly that the terminal fields of internuclear projections (eg, to striatum, pallidum, nigra, thalamus, etc) often appear patchy and highly divergent, suggesting that neighboring groups of projection cells tend to influence interdigitating clusters of postsynaptic neurons While more intricate and complex than simple point-to-point topography, however, this type arrangement should also be capable of maintaining functional specificity As discussed briefly above, it is not yet clear to what extent the inputs to the "motor" circuit from the different precentral motor fields (eg, MC, SMA, APA) are integrated in their passage through the circuit It now appears that at the level of the putamen such inputs remain segregated(ABSTRACT TRUNCATED AT 400 WORDS)

Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions.

The vertebrate brain continues to produce new neurons throughout life. In the rat hippocampus, several thousand are produced each day, many of which die within weeks. Associative learning can enhance their survival; however, until now it was unknown whether new neurons are involved in memory formation. Here we show that a substantial reduction in the number of newly generated neurons in the adult rat impairs hippocampal-dependent trace conditioning, a task in which an animal must associate stimuli that are separated in time. A similar reduction did not affect learning when the same stimuli are not separated in time, a task that is hippocampal-independent. The reduction in neurogenesis did not induce death of mature hippocampal neurons or permanently alter neurophysiological properties of the CA1 region, such as long-term potentiation. Moreover, recovery of cell production was associated with the ability to acquire trace memories. These results indicate that newly generated neurons in the adult are not only affected by the formation of a hippocampal-dependent memory, but also participate in it.

Neurogenesis in the adult is involved in the formation of trace memories

Lynch, MA. Long-Term Potentiation and Memory. Physiol Rev 84: 87–136, 2004; 10.1152/physrev.00014.2003.—One of the most significant challenges in neuroscience is to identify the cellular and molecu...

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Long-Term Potentiation and Memory

A patient with selective bilateral damage to the amygdala did not acquire conditioned autonomic responses to visual or auditory stimuli but did acquire the declarative facts about which visual or auditory stimuli were paired with the unconditioned stimulus. By contrast, a patient with selective bilateral damage to the hippocampus failed to acquire the facts but did acquire the conditioning. Finally, a patient with bilateral damage to both amygdala and hippocampal formation acquired neither the conditioning nor the facts. These findings demonstrate a double dissociation of conditioning and declarative knowledge relative to the human amygdala and hippocampus.

https://science.sciencemag.org/content/sci/269/5227/1115.full.pdf

Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans

Hippocampectomy selectively disrupts discrimination reversal conditioning of the rabbit nictitating membrane response.

The effects of bilateral hippocampal and neocortical lesions were examined on acquisition and retention of classically conditioned responses based on (a) simple associations, (b) a nonconditional discrimination, and (c) a conditional discrimination in the same subjects. Results showed that combined hippocampal and neocortical damage permanently prevented (within the limits tested) both acquisition and retention of learned behavior based on the conditional discrimination but had no effect on behaviors based on the nonconditional discrimination or simple associations. Neocortical lesions alone had no effect on either conditional or nonconditional discriminative responding, but they did temporarily disrupt acquisition and retention of behavior dependent on CS-CS (two conditioned stimuli) associations. Neither lesion affected learned behaviors mediated by CS-US (conditioned stimulus and unconditioned stimulus) associations. Thus, results showed that hippocampal damage selectively disrupted learned conditional behaviors and also revealed that central nervous system control of conditional discrimination performance, within-compound associations, and CS-US associations is mediated by different neural mechanisms.

Hippocampectomy disrupts acquisition and retention of learned conditional responding.

The effect of bilateral lesions of the retrosplenial cortex on discrimination reversal learning of the rabbit nictitating membrane response was examined. Results showed that animals with such lesions were not impaired in their ability to acquire a cross-modality discrimination, but were severely impaired in their ability to reverse the discrimination once it was learned. All animals failed at the reversal phase of the task because they displayed high levels of conditioned responding to both the CS+ and the CS-. Thus bilateral damage to the retrosplenial cortex results in deficits in reversal learning that are highly similar to those observed after bilateral hippocampectomy. These findings are interpreted within a conceptual framework that characterizes multisynaptic projections from the hippocampus to the retrosplenial cortex, and ultimately to the cerebellum, as responsible for the behavioral expression of learning-related changes in hippocampal pyramidal cell activity.

Lesions of the retrosplenial cortex produce deficits in reversal learning of the rabbit nictitating membrane response: implications for potential interactions between hippocampal and cerebellar brain systems.

Short-term effects of dopamine-depleting brain lesions on spontaneous activity of striatal neurons: relation to local dopamine concentration and behavior.

The effects of bilateral hippocampectomy on the topography, or shape, of conditioned nictitating membrane (NM) responses were examined during four learning tasks: one-tone delay conditioning, unpaired extinction, two-tone discrimination, and reversal of two-tone discrimination. Results showed that hippocampal ablation altered conditioned NM response topography only during reversal learning and not during the other training paradigms. In addition, the shapes of learning curves for hippocampectomized animals were different from those of control animals during reversal conditioning but not during the other paradigms. The implications of these findings with respect to unit-recording studies of hippocampal cellular activity during classical conditioning of the NM response are discussed.

William B. Orr

Papers

Hippocampectomy selectively disrupts discrimination reversal conditioning of the rabbit nictitating membrane response.

Hippocampectomy disrupts acquisition and retention of learned conditional responding.

Lesions of the retrosplenial cortex produce deficits in reversal learning of the rabbit nictitating membrane response: implications for potential interactions between hippocampal and cerebellar brain systems.

Short-term effects of dopamine-depleting brain lesions on spontaneous activity of striatal neurons: relation to local dopamine concentration and behavior.

Hippocampectomy disrupts the topography of conditioned nictitating membrane responses during reversal learning.