Title: Entorhinal-hippocampal a speculative view of their fund/on
Abstract: On the basis of neuroanatomical studies, the entorhmal cortex (EC) has long been regarded as a relay station that provides the major source of afferent input to the hippocampus. The perforant path input to the dentate gyrus from layer H has traditionally been regarded as the major pathway by which information is transferred. However, electrophysiological studies are now indicat- ing that other elements of the perforant path that project directly to CA1 and CA3 are more important than thought previously, and that the properties of different neuronal elements in the EC may determine the way in which information is passed on to and processed by the hippocampus. This article summarizes some of the properties of synaptic transmission in the EC and speculates on how frequency-dependent changes in transmission may be involved in the pre- and post- processing of hippocampal information by the EC. The entorhinal cortex (EC) forms a major part of what is termed the parahippocampal area in lower species and the parahippocampal gyrus in primates, including humans. Phylogenetically, it is a relatively old struc- ture and is, in some respects, transitional between the hippocampus and neocortex. The importance of the EC, particularly as the major source of afferent input to the hippocampus, has long been recognized by neuroanatomists, who have paid much attention to its synaptic connections, but our knowledge of the physiology of the EC has lagged far behind. This is surprising in view of persistent conclusions that the EC is pivotal in the control of hippocampal function and may be a primary target in several disorders of the CNS. There is now abundant evidence that the EC shows some of the earliest and most severe pathological alterations in Alzheimer's disease. Antemortem stud- ies have indicated atrophy of the parahippocampal gyrns in Alzheimer's patients. Postmortem studies of brains of Alzheimer's patients by (among others) Braak and Braak 1 have shown that intraneuronal neurofibrillary changes are detectable in the EC at a very early stage of the disease, and these may even represent a 'clinically silent' phase of the illness. A graphical summary of the data presented by these authors is shown in Fig. 1. Neurones of layer II and layer IV are particularly susceptible to degeneration, and neurones of the subiculum and CA1 may also be preferentially lost 2. These neuronal losses are ac- companied by loss of membrane receptors of diverse types, including glutamate [N-methyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4-isox- azole propionic acid (AMPA)], GABAA, 5-HT, neuro- tensin, benzodiazepine, adenosine and opioid recep- tors a. It has been suggested that the degeneration of much of the neuronal architecture of the EC destroys a large functional part of hippocampal input and output, and that this results in the memory and cognitive deficits associated with Alzheimer's disease 2. Other dementing disorders, such as Pick's disease and Lewy body dementia, also show severe patho- logical changes in the EC. In addition, the classical study of Hirano and Zimmerman 4 described patho- logical alterations in the 'giomerular substance of the hippocampal gyrus' (analogous to the EC) in a series of patients with Parkinson's disease, amyotrophic lateral sclerosis, Guam disease or Down syndrome. It seems likely that such lesions are involved in the symptoms of dementia that are associated with all these disorders. Other postmortem studies have implicated neuropathological disruption of the EC, perhaps during development, in schizophrenia and manic depression ~-7. Finally there is a good case for considering the EC as a focus in epilepsies involving the limbic system and temporal lobe; this is outlined in more detail below. Given the strong indications for a key role of the EC in these disorders of the CNS, it is important to determine its role in normal CNS function. In this article I wish to review physiological studies of the EC and present a speculative hypothesis concerning its processing function with respect to the hippocampus.
Publication Year: 1993
Publication Date: 1993-01-01
Language: en
Type: article
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