Biomedical subjects

Menno P Witter

Publications and source records attributed to Menno P Witter.

At least 19 recordsLinked to original sources

PubMed2006

Conjunctive representation of position, direction, and velocity in entorhinal cortex.

Grid cells in the medial entorhinal cortex (MEC) are part of an environment-independent spatial coordinate system. To determine how information about location, direction, and distance is integrated in the grid-cell network, we recorded from each principal cell layer of MEC in rats that explored two-dimensional environments. Whereas layer II was predominated by grid cells, grid cells colocalized with head-direction cells and conjunctive grid x head-direction cells in the deeper layers. All cell types were modulated by running speed. The conjunction of positional, directional, and translational information in a single MEC cell type may enable grid coordinates to be updated during self-motion-based navigation.

Animals↗

PubMed2006

Differential regional atrophy of the cingulate gyrus in Alzheimer disease: a volumetric MRI study.

Magnetic resonance imaging-based volumetric measurements provide a useful technique for quantifying in vivo regional cerebral atrophy in Alzheimer disease (AD). Histopathological studies have shown the cingulate cortex, a cytoarchitectonically heterogeneous region, to be severely affected in AD. In this study, we developed and validated a manual segmentation protocol, based on macroscopic characteristics such as gyri and sulci patterns, in order to assess volumetric changes in 4 cingulate regions of interest. Cingulate cortical volumes of 10 familial AD patients were compared with 10 age- and sex-matched controls. Inter- and intrarater reliability coefficients were high for all cingulate regions (91.9-99.4%). All 4 cingulate regions were significantly smaller (P < 0.05) in AD cases compared with controls: rostral anterior cingulate gyrus (22.5% smaller), caudal anterior cingulate gyrus (20.7% smaller), posterior cingulate gyrus (44.1% smaller), and retrosplenial cortex (21.5% smaller). The atrophy in the posterior cingulate region was significantly greater than that in other cingulate regions (P < 0.001), suggesting a higher vulnerability for this region in familial AD. Considering the functional and connectional differences of these 4 cingulate regions, detection and monitoring of their atrophy may provide insights into the natural history of AD and may help in the search for diagnostic markers for early AD.

Alzheimer Disease↗

PubMed2005

Verapamil prevents, in a dose-dependent way, the loss of ChAT-immunoreactive neurons in the cerebral cortex following lesions of the rat nucleus basalis magnocellularis.

In the present study we analysed the neuroprotective effect of the L-type voltage-dependent calcium channel antagonist verapamil on cholineacetyltransferase (ChAT)-immunoreactive neurons in the cerebral cortex of rats with bilateral electrolytic lesions of the nucleus basalis magnocellularis (NBM). Treatment with verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg/12 h i.p.) started 24 h after NBM lesions and lasted 8 days. Animals were sacrificed on day 21 after NBM-lesions. The bilateral NBM-lesions produced significant loss of ChAT-immunoreactive neurons in frontal, parietal and temporal cortex. Although the number of ChAT-positive neurons was significantly higher in NBM-lesioned animals treated with verapamil at a dose of 2.5, 5.0 and 10.0 mg/kg than in saline treated ones, the most significant effect was obtained at a dose of 5 mg/kg. This is, to our knowledge, the first report showing an inverted U-shape mode of neuroprotective action of the calcium antagonist verapamil, at morphological level in this particular model of brain damage. The demonstrated beneficial effect of verapamil treatment suggests that the regulation of calcium homeostasis during the early period after NBM lesions might be a possible treatment to prevent neurodegenerative processes in the rat cerebral cortex.

Analysis of Variance↗

PubMed2005

Presubiculum stimulation in vivo evokes distinct oscillations in superficial and deep entorhinal cortex layers in chronic epileptic rats.

The characteristic cell loss in layer III of the medial entorhinal area (MEA-III) in human mesial temporal lobe epilepsy is reproduced in the rat kainate model of the disease. To understand how this cell loss affects the functional properties of the MEA, we investigated whether projections from the presubiculum (prS), providing a main input to the MEA-III, are altered in this epileptic rat model. Injections of an anterograde tracer in the prS revealed bilateral projection fibers mainly to the MEA-III in both control and chronic epileptic rats. We further examined the prS-MEA circuitry using a 16-channel electrode probe covering the MEA in anesthetized control and chronic epileptic rats. With a second 16-channel probe, we recorded signals in the hippocampus. Current source density analysis indicated that, after prS double-pulse stimulation, afterdischarges in the form of oscillations (20-45 Hz) occurred that were confined to the superficial layers of the MEA in all epileptic rats displaying MEA-III neuronal loss. Slower oscillations (theta range) were occasionally observed in the deep MEA layers and the dentate gyrus. This kind of oscillation was never observed in control rats. We conclude that dynamical changes occur in an extensive network within the temporal lobe in epileptic rats, manifested as different kinds of oscillations, the characteristics of which depend on local properties of particular subareas. These findings emphasize the significance of the entorhinal cortex in temporal lobe epilepsy and suggest that the superficial cell layers could play an important role in distributing oscillatory activity.

Animals↗

PubMed2005

Disorder-specific neuroanatomical correlates of attentional bias in obsessive-compulsive disorder, panic disorder, and hypochondriasis.

CONTEXT: Attentional bias to disease-relevant emotional cues is considered to be pathogenetically relevant in anxiety disorders. OBJECTIVE: To investigate functional neural correlates and disease specificity of attentional bias across different anxiety disorders. DESIGN: A cognitive and emotional Stroop task, consisting of congruent and incongruent color words, obsessive-compulsive disorder (OCD)-related and panic-related negative words, and neutral words, was used in 3 patient groups and a control group during functional magnetic resonance imaging. SETTING: Academic outpatient department for anxiety disorders. PATIENTS AND PARTICIPANTS: Medication-free patients with OCD (n = 16), panic disorder (PD) (n = 15), and hypochondriasis (n = 13) and 19 controls. MAIN OUTCOME MEASURE: Voxel-wise analyses of cerebral blood flow changes for contrasts of interest (incongruent vs congruent color words, OCD-related vs neutral words, and panic-related vs neutral words) within and between groups. RESULTS: During incongruent vs congruent color naming, all patient groups recruited additional posterior brain regions relative to controls, but performance was impaired only in OCD. In OCD, color naming OCD-related, but not PD-related, words correlated with increased activation of frontal-striatal and temporal regions, although performance was unimpaired. In contrast, in PD, increased frontal-striatal involvement was found during color naming both OCD-related and panic-related words. In PD, color naming panic-related words was slowed and correlated with increased activation of the right amygdala and hippocampus. Patients with hypochondriasis showed a similar activation pattern to patients with PD. CONCLUSIONS: Our results support the hypothesis of increased distractibility for irrelevant information in patients with OCD, PD, and hypochondriasis associated with frontal-striatal and limbic involvement compared with controls. Although patients with OCD did not display an attentional bias in behavior relative to controls, there was a clear, specific neural response during color naming OCD-related words, involving mainly ventral brain regions. In contrast, generalized emotional interference effects were found in PD and hypochondriasis, involving ventral and widespread dorsal brain regions, reflecting not only unconscious emotional stimulus processing but also increased cognitive elaboration.

Adult↗

PubMed2004

Amygdala activity in obsessive-compulsive disorder with contamination fear: a study with oxygen-15 water positron emission tomography.

Previous imaging studies of obsessive-compulsive symptom states have implicated frontal-striatal and limbic regions in the pathophysiology of obsessive-compulsive disorder (OCD). Functional imaging studies, however, have yielded inconsistent results, presumably due to methodological differences (patient inclusion criteria, stimulus paradigm, imaging technique, and absence of control groups). In the present study, randomized presentation of contamination-related and neutral visual stimuli was used to investigate the neurophysiological correlates of contamination fear in a group of medication-free OCD patients with washing behaviors and healthy controls. A total of 21 subjects (11 OCD patients and 10 healthy controls) were scanned using H(2)(15)O positron emission tomography (PET). Subjects were presented with pictures of clean and dirty surroundings and were requested to make indoor/outdoor decisions to control for attention differences. State anxiety and obsessionality were rated after each scan using visual analogue scales. Main effects of stimulus type (contamination vs. neutral) were found in bilateral occipital cortex in both groups. A significant group interaction effect was observed in the left amygdala reflecting enhanced activity in response to contamination stimuli in OCD patients. Sensitization effects were observed in the right amygdala in the OCD group; these paralleled an increase in levels of distress and obsessionality as well as a decrease in dorsolateral prefrontal activity. The findings of the present study are consistent with the hypothesis of decreased frontal-striatal control of limbic structures, specifically the amygdala, resulting in an inadequate fear response in OCD patients with contamination fear.

Adult↗

PubMed2004

Neurophysiological correlates of habituation during exposure in spider phobia.

Imaging studies using symptom-provocation paradigms in specific phobia have yielded contradictory results, possibly reflecting a failure to account for habituation processes. Given that a single session of exposure in vivo can result in significant improvement in specific phobia, we used prolonged exposure to phobic stimuli to identify CNS regions showing habituation. Eighteen subjects (12 with spider phobia, 6 healthy controls) underwent H(2)(15)O-positron emission tomography while being continuously presented with pictures of spiders or butterflies. Results showed main effects (spiders>butterflies) in the phobia group in the left fusiform gyrus (FG) and the right parahippocampal gyrus (PHG), with bilateral perirhinal cortex and right limbic areas approaching significance. Group x condition effects were found in the right amygdala and PHG. During spider scans, large habituation effects were observed in the anterior medial temporal lobe (MTL) bilaterally. Regression analyses demonstrated that state anxiety was correlated with activity in left amygdala, bilateral perirhinal cortex, right FG, and periaquaductal grey; by contrast, phobic fear was only associated with right-sided hippocampal activity. We conclude that prolonged exposure to phobic stimuli is associated with a significant decrease in bilateral anterior MTL regional cerebral blood flow. Right anterior MTL, identified when comparing phobic vs. neutral stimuli and habituation to phobic vs. neutral stimuli in the phobia group, implicates this region in phobic fear. Analyses of covariance suggest a further functional segregation with state anxiety being linked to enhanced activity in amygdala, perirhinal cortex, and tegmentum, and phobic fear with enhanced right hippocampal activity, suggesting a neuroanatomical differentiation between emotional-vegetative and cognitive aspects of (phobic) fear.

Adult↗

PubMed2004

Spatial representation in the entorhinal cortex.

As the interface between hippocampus and neocortex, the entorhinal cortex is likely to play a pivotal role in memory. To determine how information is represented in this area, we measured spatial modulation of neural activity in layers of medial entorhinal cortex projecting to the hippocampus. Close to the postrhinal-entorhinal border, entorhinal neurons had stable and discrete multipeaked place fields, predicting the rat's location as accurately as place cells in the hippocampus. Precise positional modulation was not observed more ventromedially in the entorhinal cortex or upstream in the postrhinal cortex, suggesting that sensory input is transformed into durable allocentric spatial representations internally in the dorsocaudal medial entorhinal cortex.

Action Potentials↗

PubMed2004

Input from the presubiculum to dendrites of layer-V neurons of the medial entorhinal cortex of the rat.

The entorhinal cortex (EC) and the hippocampus are reciprocally connected. Neurons in the superficial layers of EC project to the hippocampus, whereas deep entorhinal layers receive return connections. In the deep layers of EC, pyramidal neurons in layer V possess apical dendrites that ascend towards the cortical surface through layers IIII and II. These dendrites ramify in layer I. By way of their apical dendrites, such layer-V pyramidal cells may be exposed to input destined for the superficial entorhinal neurons. A specific and dense fiber projection that typically ends in superficial entorhinal layers of the medial EC originates in the presubiculum. To investigate whether apical dendrites of deep entorhinal pyramidal neurons indeed receive input from this projection, we injected the anterograde tracer PHA-L in the presubiculum or we lesioned the presubiculum, and we applied in the same experiments the tracer Neurobiotin trade mark pericellularly in layer V of the medial EC of 17 rats. PHA-L labeled presubiculum axons in the superficial layers apposing apical segments of Neurobiotin labeled layer-V cell dendrites were studied with a confocal fluorescence laserscanning microscope. Axons and dendrites were 3D reconstructed from series of confocal images. In cases in which the presubiculum had been lesioned, material was investigated in the electron microscope. At the confocal fluorescence microscope level we found numerous close contacts, i.e. appositions of boutons on labeled presubiculum fibers with identified dendrites of layer-V neurons. In the electron microscope we observed synapses between degenerating axon terminals and spines on dendrites belonging to layer-V neurons. Hence we conclude that layer-V neurons receive synaptic contacts from presubiculum neurons. These findings indicate that entorhinal layer-V neurons have access to information destined for the superficial layers and eventually the hippocampal formation. At the same time, they have access to the hippocampally processed version of that information.

Animals↗

PubMed2004

Cytoarchitectonic characterization of the parahippocampal region of the guinea pig.

The cytoarchitectonic features of the parahippocampal region (PHR) in the guinea pig are described, based on coronal, horizontal, and sagittal 50-microm sections stained for Nissl substance, zinc, parvalbumin, or calbindin. We differentiate between perirhinal (PRC), postrhinal (POR), and entorhinal (ERC) cortices. PRC is divided into areas 35 and 36 occupying the fundus and the dorsal bank of the rhinal fissure, respectively. POR is located caudal to the PRC. POR and area 36 show a dense, clustered cellular layer II and a thinner layer III in comparison to the adjacent neocortex, and they differ from each other with respect to the orientation of the somata of layer VI neurons. Area 35 is characterized by a thin layer II that is not very different from layer III. Layer IV is (dys)granular in area 36 and POR, and is absent in area 35 and ERC. ERC, located ventromedial to the PRC and POR, is subdivided in six fields, of which field 5 is adjacent to area 35. In both area 35 and field 5, no clear differentiation between layers II and III is present. Field 5 shows a darker cellular stain and exhibits a cell-free zone or lamina dissecans between layers III and V. Medial to field 5, an area characterized by large cell clusters in layer II is designated field 4. The latter field is replaced by field 3 rostromedially, which also typically shows clustering of layer II neurons. These cell clusters in field 3, however, are much more constant in size in spacing compared to those in field 4. The caudomedial portion of ERC is subdivided into fields 1, 1', and 2. The latter, characterized by a homogeneous distribution of neurons in all layers with large darkly stained neurons in layer V is positioned rostral to field 1 and caudomedial to fields 4 and 5. In field 1, layers V and VI are thinner, and layer II neurons are smaller then in field 1' and field 2. We conclude that the architectonic features of the guinea pig PHR are comparable to those described in other mammals, particularly the rat.

Animals↗

PubMed2004

Common pathway in the medial temporal lobe for storage and recovery of words as revealed by event-related functional MRI.

Lesion studies have provided compelling evidence that episodic memory is dependent on the integrity of the medial temporal lobe (MTL). This role of the MTL in episodic memory has been supported by several neuroimaging studies during both episodic encoding and retrieval. After two meta-analyses of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies, we investigated a possible dissociation within the MTL memory system in relation to encoding and retrieval processes. Based on previous reports that specifically related the function of the MTL in episodic memory to successful encoding and actual recovery of information, we applied event-related fMRI to compare successful encoding of words (ES) directly with successful recognition of those same words (RS). Our results did not indicate a clear dissociation between encoding and retrieval activations in the MTL. Instead, a region in the left MTL, covering the parahippocampal cortex and hippocampal formation, which was activated during ES almost completely overlapped with the area that was activated during RS. An additional region in the left anterior MTL, including the entorhinal cortex, was found to be activated exclusively during ES. Research has indicated that a large percentage of cells in this region are particularly sensitive to the relative novelty of stimuli. Our results, therefore, suggest that the parahippocampal/hippocampal region is involved in the formation and subsequent reactivation of memory traces, whereas the activity observed in the entorhinal cortex may reflect elementary memory processes related to novelty detection.

Adult↗

PubMed2003

Synaptic contacts between identified neurons visualized in the confocal laser scanning microscope. Neuroanatomical tracing combined with immunofluorescence detection of post-synaptic density proteins and target neuron-markers.

The axons of neurons in the CNS with their delicate ramification patterns and terminal boutons can be visualized with conventional neuroanatomical techniques with a high degree of accuracy. Whether identified terminal boutons form synaptic contacts with target neurons identified by a second and different marker needs resolution beyond that offered by conventional light microscopy. The morphological elements associated with synaptic connectivity consist of specialized pre- and post-synaptic junctional complexes known as the pre- and post-synaptic densities. Electron microscopy of these junctional complexes consumes much time and resources. In an attempt to increase the speed with which we can analyze networks of neurons we developed a high-resolution triple-fluorescence approach including neuroanatomical tracing, immunofluorescence, confocal laserscanning and 3D-computer reconstruction to pinpoint at the light microscopic level the three elements involved in synaptic connectivity: afferent fibers and their terminal boutons, close apposition with neurons identified by the presence of a fluorescent marker, and sandwiched in between a post-synaptic density marker. We used morphological criteria for the detection of axon terminals (swellings on fibers). Antibodies against ProSAP2/Shank3, a post-synaptic density-associated scaffolding protein, were used to pinpoint the location of the synaptic junctions. The results show the existence of sandwich-like configurations: pre-synaptic fiber, ProSAP2/Shank3, post-synaptic neuron. Thus we feel that we can minimize (and perhaps completely eliminate) the need for electron microscopy and hence dramatically increase the overall efficiency of neuroanatomical tracing and network analysis.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Topographical and laminar organization of subicular projections to the parahippocampal region of the rat.

In this study, we analyzed in detail the topographic organization of the subiculoparahippocampal projection in the rat. The anterograde tracers Phaseolus vulgaris leucoagglutinin-L and biotinylated dextran amine were injected into the subiculum at different septotemporal and transverse levels. Deep layers of the ento-, peri-, and postrhinal cortices are the main recipients of subicular projections, but in all cases we noted that a small fraction of the projections also terminates in the superficial layers II and III. Analysis of the fiber patterns in the parahippocampal region revealed a topographic organization, depending on the location of the cells of origin along both the transverse and the septotemporal axes of the subiculum. Projections originating from subicular cells close to CA1, i.e., proximal part of subiculum, terminate exclusively in the lateral entorhinal cortex and in the perirhinal cortex. In contrast, projections from cells closer to the subiculum-presubiculum border, i.e., distal part of subiculum, terminate in the medial entorhinal cortex and in the postrhinal cortex. In addition, cells in septal portions of the subiculum project to a lateral band of entorhinal cortex parallel to the rhinal sulcus and to peri- or postrhinal cortices, whereas cells in more temporal portions project to more medial parts of the entorhinal cortex. These results indicate that subicular projections to the parahippocampal region precisely reciprocate the known inputs from this region to the hippocampal formation. We thus suggest that the reciprocal connectivity between the subiculum and the parahippocampal region is organized as parallel pathways that serve to segregate information flow and thus maintain the identity of processed information. Although this parallel organization is comparable to that of the CA1-parahippocampal projections, differences exist with respect to the degree of collateralization.

Animals↗

PubMed2003

Morphological and numerical analysis of synaptic interactions between neurons in deep and superficial layers of the entorhinal cortex of the rat.

Neurons providing connections between the deep and superficial layers of the entorhinal cortex (EC) constitute a pivotal link in the network underlying reverberation and gating of neuronal activity in the entorhinal-hippocampal system. To learn more of these deep-to-superficial neurons and their targets, we applied the tracer Neurobiotin pericellularly in layer V of the medial EC of 12 rats. Labeled axons in the superficial layers were studied with light and electron microscopy, and their synaptic organization recorded. Neurobiotin-labeled layer V neurons displayed "Golgi-like" staining. Two major cell types were distinguished among these neurons: (1) pyramidal neurons with apical spiny dendrites traversing all layers and ramifying in layer I, and (2) horizontal neurons with dendrites confined to the deep layers. Labeled axons ramified profusely in layer III, superficially in layer II and deep in layer I. Analysis of labeled axon terminals in layers I-II and III showed that most synapses (95%) were asymmetrical. Of these synapses, 56% occurred with spines (presumably belonging to principal neurons) and 44% with dendritic shafts (presumably interneurons). A small fraction of the synapses (5%) was of the symmetrical type. Such synapses were mainly seen on dendritic shafts. We found in two sections a symmetrical synapse on a spine. These findings suggest that the deep to superficial projection is mainly excitatory in nature, and that these fibers subserve both excitation and feed-forward inhibition. There is an additional, much weaker, inhibitory component in this projection, which may have a disinhibitory effect on the entorhinal network in the superficial layers.

Animals↗

PubMed2003

Deficits of memory, executive functioning and attention following infarction in the thalamus; a study of 22 cases with localised lesions.

The thalamus plays a crucial role in memory, executive functioning and attention. It remains, however, unclear whether thalamic structures have specific roles in each of these functions. We tested 22 cases of thalamic infarction, proven with MR imaging, using experimental and established neuropsychological tests. We performed a lesion-overlap study in standardised stereotactic space of patients sharing a certain deficit, corrected for the lesion distribution of patients without such deficits and determined the regions of interest using an atlas of the human thalamus. We checked for additional, non-thalamic, damage and for deficient comprehension and perception that would preclude interpretation of the results. Non-thalamic damage such as white matter lesions, hippocampal atrophy, sulcal widening and infarctions occur significantly more often in patients aged over 60. The patients with additional damage overlapped to a major degree with those who showed loss of orientation, or lack of comprehension of the test requirements. In the 10 patients judged 'clean', we observed a deficit of episodic long-term memory with relative sparing of intellectual capacities and short-term memory when the mammillo-thalamic tract was damaged. Lesions including the medial dorsal nucleus, midline nuclei and/or intralaminar nuclei accompany executive dysfunctioning. Reduced simple processing speed and attention are associated with age, but not with a particular structure in the thalamus. Complex attention deficits follow damage to the intralaminar nuclei.We conclude that the analysis of structure-function relationships must take into account extra-structure damage which may explain cognitive deficits. Separate thalamic structures are involved in memory, executive functioning and attention.

Adult↗

PubMed2003

A cytoarchitectonic study of the hippocampal formation of the tree shrew (Tupaia belangeri).

Tree shrews constitute an interesting animal model to study the impact of stress or aging on the hippocampal formation, a brain structure known to be affected under such environmental or internal influences. To perform detailed investigations of the hippocampal formation, adequate knowledge of its anatomy should be present. Until now, the hippocampal formation of the tree shrew has not yet been studied extensively. The main objective of this study, therefore, was to describe the subfield boundaries in various levels of the dorsoventral hippocampal axis of the tree shrew (Tupaia belangeri) in detail. The secondary aim was to clarify whether a separate CA2 field can actually be distinguished in the tree shrew hippocampus, a fact that was denied in former reports. In addition, we aimed at investigating whether or not a CA4 subfield can be identified in the tree shrew's hippocampus. The immunocytochemical distribution of microtubule-associated protein 2 and the calcium-binding proteins, parvalbumin and calbindin, and the characteristics of Nissl staining in adjacent sections were compared. Because of the rather dorsoventral orientation of the long hippocampal axis in tree shrews, staining patterns were analyzed mainly in horizontal sections. The subiculum and the hippocampal CA1 and CA3 areas were easily identified. Moreover, we were able to demonstrate the existence of a distinct CA2 subfield in the tree shrew's Ammon's horn, contrary to previous reports. However, our results indicate that a CA4 field in the tree shrew hippocampal formation cannot be identified with the methods that we used. Therefore, supposed CA4 pyramidal neurons should be included into the CA3 field.

Animals↗

PubMed2003

GAP-43 mRNA and protein expression in the hippocampal and parahippocampal region during the course of epileptogenesis in rats.

In order to reveal axonal rewiring in the hippocampal and parahippocampal regions after status epilepticus, we investigated the temporal evolution of growth-associated protein-43 (GAP-43) mRNA and protein expression in two rat models of mesial temporal lobe epilepsy (MTLE). Status epilepticus (SE) was induced by electrical stimulation of the angular bundle or by intraperitoneal kainic acid (KA) injections. Despite increased GAP-43 mRNA expression in dentate granule cells at 24 h after SE, GAP-43 protein expression in the inner molecular layer (IML) of the dentate gyrus decreased progressively after 24 h after SE in both models. Nevertheless robust mossy fiber sprouting (MFS) was evident in the IML of chronic epileptic rats. Remaining GAP-43 protein expression in the IML in chronic epileptic rats did not correlate with the extent of MFS, but with the number of surviving hilar neurons. In the parahippocampal region, GAP-43 mRNA expression was decreased in layer III of the medial entorhinal area (MEAIII) in parallel with extensive neuronal loss in this layer. There was a tendency of GAP-43 mRNA up-regulation in the presubiculum, a region that projects to MEAIII. With regard to this parahippocampal region, however, changes in GAP-43 mRNA expression were not followed by protein changes. The presence of the presynaptic protein GAP-43 in a neurodegenerated MEAIII indicates that fibers still project to this layer. Whether reorganization of fibers has occurred in this region after SE needs to be investigated with tools other than GAP-43.

Animals↗

PubMed2003

Electrophysiological characterization of interlaminar entorhinal connections: an essential link for re-entrance in the hippocampal-entorhinal system.

The hippocampal formation communicates with the neocortex mainly through the adjacent entorhinal cortex. Neurons projecting to the hippocampal formation are found in the superficial layers of the entorhinal cortex and are largely segregated from the neurons receiving hippocampal output, which are located in deep entorhinal layers. We studied the communication between deep and superficial entorhinal layers in the anaesthetized rat using field potential recordings, current source density analysis and single unit measurements. We found that subiculum stimulation was able to excite entorhinal neurons in deep layers. This response was followed by current sinks in superficial layers. Both responses were subject to frequency dependent facilitation, but not depression. Selective blockade of deep layer responses also abolished subsequent superficial layer responses. This clearly demonstrates a functional deep-to-superficial layer communication in the entorhinal cortex, which can be triggered by hippocampal output. This pathway may provide a means by which processed hippocampal output is integrated or compared with new incoming information in superficial entorhinal layers, and it constitutes an important link in the process of re-entrance of activity in the hippocampal-entorhinal network, which may be important for consolidation of memories or retaining information for short periods.

6-Cyano-7-nitroquinoxaline-2,3-dione↗