Progress in Neuro-Psychopharmacology and Biological Psychiatry
Entorhinal cortex and cognition
Introduction
Since the historical description of the case H.M. 50 years ago (Scoville and Milner, 1957), a tremendous effort has been dedicated to the study of the medial temporal lobe and its role in learning and memory, in human as well as in non human primates and rodents. The involvement of this area in episodic memory has been convincingly demonstrated, and the unravelling of the underlying mechanisms is rapidly progressing (e.g. Eichenbaum, 2004). The brain structures composing the medial temporal lobe, that is the hippocampus (Ammon's horn and dentate gyrus), the entorhinal and perirhinal cortices are heavily interconnected and their respective contribution to memory is difficult to disentangle. In particular, the Entorhinal Cortex (EC) has long been viewed as a simple interface between cortical regions and the hippocampus, considering that the alteration of EC or hippocampus is functionally equivalent. As illustrated below, this is indeed often the case, indicating that both structures belong to the same processing chain. However, anatomical data demonstrate that the hippocampus and the EC have distinct, although partially overlapping, domains of connectivity. Damage to these brain areas may therefore induce distinct functional and cognitive brain states. Numerous reviews concerning the role of the hippocampus in cognition have been published (e.g. Atallah et al., 2004, Eichenbaum, 2004, Squire, 1992). The present article, based on rodent studies, aims at illustrating cognitive processes which may depend on the EC and downstream areas other than the hippocampus. Various human brain diseases involve pathologies of the EC and are characterised by both common and distinctive cognitive alterations. Improving our knowledge of the cognitive consequences of EC damage in animals may therefore be useful for the understanding of these diseases.
Section snippets
The EC in diseased human brain
In the human brain, the EC (Brodmann areas 28 and 34) is located within the ventromedial portion of the temporal lobe, caudal to prepiriform and piriform cortices, and rostral to the parasubiculum. The EC reliably appears as a shiny verrucuous surface located below the tentorial notch. At this level, the brain is unprotected by dura from this indentation of the tentorium cerebelli, and it was suggested that the EC may suffer mechanical damage in case of traumas or increased intracranial
Anatomy of the EC in rodents
The rodent entorhinal cortex is located at the caudal end of the temporal lobe. It is usually divided into a medial (MEC) and a lateral (LEC) regions. The entorhinal cortex is intermediate in structure between the six-layered neocortex and the two-layered allocortex as a distinguishing characteristic of the EC is the presence of the lamina dissecans which is characterised by the lack of cell bodies where layer IV should be. For this reason, the EC is sometimes classified as a periallocortex.
The
Cognitive deficits in EC-lesioned animals
A basic description of the procedures used for the assessment of cognitive processes mediated by the hippocampal formation is shown in Table 1.
Acknowledgement
The authors wish to thank Dr. Alain Marchand for his careful reading of the manuscript.
References (170)
- et al.
Differences in synaptic transmission between medial and lateral components of the perforant path
Brain Res
(1984) - et al.
Further evidence of abnormal cytoarchitecture of the entorhinal cortex in schizophrenia using spatial point pattern analyses
Biol Psychiatry
(1997) - et al.
Hippocampus, cortex, and basal ganglia: insights from computational models of complementary learning systems
Neurobiol Learn Mem
(2004) - et al.
Hippocampal unit–behavior correlations during classical conditioning
Brain Res
(1980) - et al.
Odor regulates the expression of the mitogen-activated protein kinase phosphatase gene hVH-5 in bilateral entorhinal cortex-lesioned rats
Brain Res Mol Brain Res
(2000) - et al.
Morphometric studies of the entorhinal cortex in neuropsychiatric patients and controls: clusters of heterotopically displaced lamina II neurons are not indicative of schizophrenia
Schizophr Res
(1998) - et al.
Spatial location learning in mice with ibotenate lesions of entorhinal cortex or subiculum
Neurobiol Learn Mem
(1995) - et al.
Aspiration lesions of rat ventral hippocampus disinhibit responding in conditioned suppression or extinction, but spare latent inhibition and the partial reinforcement extinction effect
Neuroscience
(1992) - et al.
Entorhinal cortex but not hippocampal or subicular lesions disrupt latent inhibition
Neurobiol Learn Mem
(1999) - et al.
Explicit memory, procedural learning and lexical priming in Alzheimer's disease
Cortex
(1994)
Preferential neuronal loss in layer III of the entorhinal cortex in patients with temporal lobe epilepsy
Epilepsy Res
Hippocampus: cognitive processes and neural representations that underlie declarative memory
Neuron
Modelling cognitive dysfunctions with bilateral injections of ibotenic acid into the rat entorhinal cortex
Neuroscience
Introduction to temporal lobe epilepsy
Epilepsy Res
Associative deficit accounts of disrupted latent inhibition and blocking in schizophrenia
Neurosci Biobehav Rev
Limbic pathology in schizophrenia: the entorhinal region—a morphometric study
Biol Psychiatry
Odor increases [3H]phorbol dibutyrate binding to protein kinase C in olfactory structures of rat brain
Effect of entorhinal cortex lesion. Brain Res
Bicuculline administration into basolateral amygdala facilitates trace conditioning of odor aversion in the rat
Neurobiol Learn Mem
Neuroanatomical and functional specificity of the basolateral amygdaloid nucleus in taste-potentiated odor aversion
Neurobiol Learn Mem
Effects of postoperative housing conditions on functional recovery in rats with lesions of the hippocampus, subiculum, or entorhinal cortex
Neurobiol Learn Mem
Spatial memory, habituation, and reactions to spatial and nonspatial changes in rats with selective lesions of the hippocampus, the entorhinal cortex or the subiculum
Behav Brain Res
Effects of unilateral entorhinal cortex lesion and ganglioside GM1 treatment on performance in a novel water maze task
Neurobiol Learn Mem
Reduced prepulse inhibition in rats with entorhinal cortex lesions
Behav Brain Res
Interictal perceptual function in epilepsy
Epilepsy Behav
Evidence for recovery of spatial learning following entorhinal cortex lesions in mice
Brain Res
Quinolinic acid lesion of the rat entorhinal cortex pars medialis produces selective amnesia in allocentric working memory (WM), but not in egocentric WM
Behav Brain Res
Different molecular cascades in different sites of the brain control memory consolidation
Trends Neurosci
Influence of the entorhinal cortex on accumbal and striatal dopaminergic responses in a latent inhibition paradigm
Neuroscience
The effects of lesions of the entorhinal cortex and the horizontal nucleus of the diagonal band of broca upon performance of a spatial location recognition task
Behav Brain Res
Asymmetrical increases in dopamine turn-over in the nucleus accumbens and lack of changes in locomotor responses following unilateral dopaminergic depletions in the entorhinal cortex
Behav Brain Res
Electrolytic lesions of the fimbria/fornix, dorsal hippocampus, or entorhinal cortex produce anterograde deficits in contextual fear conditioning in rats
Neurobiol Learn Mem
Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats
Behav Brain Res
Dorsal hippocampal lesions: effects of preconditioning CS preexposure on flavor aversion
Behav. Biology
Effects of CS preexposure on avoidance learning in rats with hippocampal lesions
J. Comp. Phys. Psych.
Cytoarchitecture of the entorhinal cortex in schizophrenia
Am J Psychiatry
The hippocampal formation
Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia
Arch Gen Psychiatry
Trace conditioning and the hippocampus: the importance of contiguity
J Neurosci
Contextual fear conditioning is disrupted by lesions of the subcortical, but not entorhinal, connections to the hippocampus
Exp Brain Res
The role of the entorhinal cortex in two forms of spatial learning and memory
Exp Brain Res
Selective cytotoxic lesions of the retrohippocampal region produce a mild deficit in social recognition memory
Exp Brain Res
Lesion of the lateral entorhinal cortex amplifies odor-induced expression of c-fos, junB, and zif 268 mRNA in rat brain
Synapse
Electrophysiological and pharmacological characterization of the direct perforant path input to hippocampal area CA3
J Neurophysiol
Acquisition of a complex place task in rats with selective ibotenate lesions of hippocampal formation: combined lesions of subiculum and entorhinal cortex versus hippocampus
Behav. Neurosc
On areas of transition between entorhinal allocortex and temporal isocortex in the human brain. Normal morphology and lamina-specific pathology in Alzheimer's disease
Acta Neuropathol
Pathological changes in the parahippocampal region in select non-Alzheimer's dementias
Attention, configuration, and hippocampal function
Hippocampus
Perirhinal and postrhinal cortices of the rat: a review of the neuroanatomical literature and comparison with findings from the monkey brain
Hippocampus
Cortical afferents of the perirhinal, postrhinal, and entorhinal cortices of the rat
J Comp Neurol
The parahippocampal region: corticocortical connectivity
Ann N Y Acad Sci
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