There has been considerable debate as to whether the hippocampus and perirhinal cortex may subserve both memory and perception. We administered a series of oddity tasks, in which subjects selected the odd stimulus from a visual array, to amnesic patients with either selective hippocampal damage (HC group) or more extensive medial temporal damage, including the perirhinal cortex (MTL group). All patients performed normally when the stimuli could be discriminated using simple visual features, even if faces or complex virtual reality scenes were presented. Both patient groups were, however, severely impaired at scene discrimination when a significant demand was placed on processing spatial information across viewpoint independent representations, while only the MTL group showed a significant deficit in oddity judgments of faces and objects when object viewpoint independent perception was emphasized. These observations provide compelling evidence that the human hippocampus and perirhinal cortex are critical to processes beyond long-term declarative memory and may subserve spatial and object perception, respectively.

Studies in rats and non-human primates suggest that medial temporal lobe (MTL) structures play a role in perceptual processing, with the hippocampus necessary for spatial discrimination, and the perirhinal cortex for object discrimination. Until recently, there was little convergent evidence for analogous functional specialisation in humans, or for a role of the MTL in processes beyond long-term memory. A recent series of novel human neuropsychological studies, however, in which paradigms from the animal literature were adapted and extended, have revealed findings remarkably similar to those seen in rats and monkeys. These experiments have demonstrated differential effects of distinct stimulus categories on performance in tasks for which there was no explicit requirement to remember information across trials. There is also accruing complementary evidence from functional neuroimaging that MTL structures show differential patterns of activation for scenes and objects, even on simple visual discrimination tasks. This article reviews some of these key studies and discusses the implications of these new findings for existing accounts of memory. A non-modular view of memory is proposed in which memory and perception depend upon the same anatomically distributed representations (emergent memory account). The limitations and criticisms of this theory are discussed and a number of outstanding questions proposed, including key predictions that can be tested by future studies.

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Investigations of memory in rats and nonhuman primates have demonstrated functional specialization within the medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampal formation and underlying entorhinal, perirhinal, and parahippocampal cortices. Most studies in humans, however, especially in patients with brain damage, suggest that the human MTL is a unitary memory system supporting all types of declarative memory, our conscious memory for facts and events. To resolve this discrepancy, amnesic patients with either selective hippocampal damage or more extensive MTL damage were tested on variations of an object discrimination task adapted from the nonhuman primate literature. Although both groups were equally impaired on standard recallbased memory tasks, they exhibited different profiles of performance on the object discrimination test, arguing against a unitary view of MTL function. Cases with selective hippocampal damage performed normally, whereas individuals with broader MTL lesions were impaired. Furthermore, deficits in this latter group were related not to the number of discriminations to be learned and remembered, but to the degree of "feature ambiguity," a property of visual discriminations that can emerge when features are part of both rewarded and unrewarded stimuli. These findings resolve contradictions between published studies in humans and animals and introduce a new way of characterizing the impairments that arise after damage to the MTL.

The medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampus and underlying entorhinal, perirhinal and parahippocampal cortex, is traditionally believed to be part of a unitary system dedicated to declarative memory. Recent studies, however, demonstrated perceptual impairments in amnesic individuals with MTL damage, with hippocampal lesions causing scene discrimination deficits, and perirhinal lesions causing object and face discrimination deficits. The degree of impairment on these tasks was influenced by the need to process complex conjunctions of features: discriminations requiring the integration of multiple visual features caused deficits, whereas discriminations that could be solved on the basis of a single feature did not. Here, we address these issues with functional neuroimaging in healthy participants as they performed a version of the oddity discrimination task used previously in patients. Three different types of stimuli (faces, scenes, novel objects) were presented from either identical or different viewpoints. Consistent with studies in patients, we observed increased perirhinal activity when participants distinguished between faces and objects presented from different, compared to identical, viewpoints. The posterior hippocampus, by contrast, showed an effect of viewpoint for both faces and scenes. These findings provide convergent evidence that the MTL is involved in processes beyond long-term declarative memory and suggest a critical role for these structures in integrating complex features of faces, objects, and scenes into view-invariant, abstract representations.

Excitatory amino-acid carrier 1 (EAAC1) is a high-affinity Na+-dependent L-glutamate/D,L-aspartate cell-membrane transport protein. It is expressed in brain as well as several non-nervous tissues. In brain, EAAC1 is the primary neuronal glutamate transporter. It has a polarized distribution in cells and mainly functions perisynaptically to transport glutamate from the extracellular environment. In the kidney it is involved in renal acidic amino-acid re-absorption and amino-acid metabolism. Here we describe the identification and characterization of an EAAC1-associated protein, GTRAP3-18. Like EAAC1, GTRAP3-18 is expressed in numerous tissues. It localizes to the cell membrane and cytoplasm, and specifically interacts with carboxy-terminal intracellular domain of EAAC1. Increasing the expression of GTRAP3-18 in cells reduces EAAC1-mediated glutamate transport by lowering substrate affinity. The expression of GTRAP3-18 can be upregulated by retinoic acid, which results in a specific reduction of EAAC1-mediated glutamate transport. These studies show that glutamate transport proteins can be regulated potently and that GTRAP can modulate the transport functions ascribed to EAAC1. GTRAP3-18 may be important in regulating the metabolic function of EAAC1.

In postmenopausal women with osteoporosis, lasofoxifene at a dose of 0.5 mg per day was associated with reduced risks of nonvertebral and vertebral fractures, ER-positive breast cancer, coronary heart disease, and stroke but an increased risk of venous thromboembolic events. (ClinicalTrials.gov number, NCT00141323.)

In this review, we will discuss the idea that the hippocampus may be involved in both memory and perception, contrary to theories that posit functional and neuroanatomical segregation of these processes. This suggestion is based on a number of recent neuropsychological and functional neuroimaging studies that have demonstrated that the hippocampus is involved in the visual discrimination of complex spatial scene stimuli. We argue that these findings cannot be explained by long-term memory or working memory processing or, in the case of patient findings, dysfunction beyond the medial temporal lobe (MTL). Instead, these studies point toward a role for the hippocampus in higher-order spatial perception. We suggest that the hippocampus processes complex conjunctions of spatial features, and that it may be more appropriate to consider the representations for which this structure is critical, rather than the cognitive processes that it mediates.