SEARCH · Search PubMed

Results for “Entorhinal Cortex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,171 records · Page 65Linked to original sources

PubMed1988

Synaptic and intrinsic responses of medical entorhinal cortical cells in normal and magnesium-free medium in vitro.

1. Extracellular recordings were made from slices of hippocampus plus parahippocampal regions maintained in vitro. Field potentials, recorded in the entorhinal cortex after stimulation in the subiculum, resembled those observed in vivo. 2. Washout of magnesium from the slices resulted in paroxysmal events which resembled those occurring during sustained seizures in vivo. These events were greatest in amplitude and duration in layers IV/V of the medial entorhinal cortex and could occur both spontaneously and in response to subicular stimulation. Spontaneous seizure-like events were not prevented by severing the connections between the hippocampus and entorhinal cortex, but much smaller and shorter events occurring in the dentate gyrus were stopped by this manipulation. Both spontaneous and evoked paroxysmal events were blocked by perfusion with the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonovalerate (2-AP5). 3. Neurons in layers IV/V were characterized by intracellular recording. Injection of depolarizing current in most cells evoked a train of nondecrementing action potentials with only weak spike frequency accommodation and little or no posttrain after hyperpolarization. 4. A small number of cells displayed burst response when depolarized by positive current. The burst consisted of a slow depolarization with superimposed action potentials which decreased in amplitude and increased in duration during the discharge. The burst was terminated by a strong after hyperpolarization and thereafter, during prolonged current pulses a train of nondecrementing spikes occurred. The burst response remained if the cell was held at hyperpolarized levels but was inactivated by holding the cell at a depolarized level. 5. Depolarizing synaptic potentials could be evoked by stimulation in the subiculum. A delayed and prolonged depolarization clearly decremented with membrane hyperpolarization and, occasionally, increased with depolarization. 6. Washout of magnesium from the slices resulted in an enhancement of the late depolarization and a reversal of its voltage dependence. Eventually a single shock to the subiculum evoked a large all-or-none paroxysmal depolarization associated with a massive increase in membrane conductance. Similar events occurred spontaneously in all cells tested. The paroxysmal depolarizations, both spontaneous and evoked, were rapidly blocked by 2-AP5. 7. It is concluded that medial entorhinal cortical cells possess several intrinsic and synaptic properties which confer an extreme susceptibility to generation of sustained seizure activity.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1994

Hippocampal epileptogenesis produced by electrolytic iron deposition in the rat dentate gyrus.

Anodal current passed through a stainless-steel electrode, positioned unilaterally in the rat dentate gyrus hilus, will produce recurrent motor seizures and significant changes in the neuronal expression of several messenger RNAs (mRNAs) throughout the full bilateral extent of the hippocampus. The present study quantitatively analyzed electroencephalograms (EEGs) from rats receiving this electrolytic treatment in order to characterize the resultant hippocampal seizure activity. To examine the epileptogenic role of ferric ion deposition to that of current-induced tissue destruction, we compared steel to platinum electrodes. Adult male rats were surgically implanted with a chronic recording electrode in the CA3 region of the hippocampus, and then (contralaterally) with either an insulated steel electrode in the hilus, platinum electrode in the hilus, or steel electrode in the medial entorhinal cortex. Each rat received an anodal current through the nonrecording treatment electrode while connected to a polygraph. Currents ranged from 0.8 mA, 7 s for hilus electrodes to 2.0 mA, 20 s for entorhinal cortex electrodes. EEGs were collected from alert, unrestrained rats for up to 50 consecutive hours, and additional EEGs were recorded periodically over a 4-day period. Subjects were sacrificed and brain sections were microscopically examined for evidence of neuropathology. The results demonstrate that electrolytic deposition of iron ions in the hilus, and not merely hilus tissue destruction, produce electrographic seizure activity within 1-2 h of current passage. Seizures recurred most intensely for 2-3 h, and sporadic epileptiform activity was detected for up to 12 h. Motor seizures of class 4 or 5 were observed in all seizing rats, and were always coincident with hippocampal seizure discharges. Histological examination of brain sections from all subjects found no evidence of cell death in the contralateral hippocampus. The dentate gyrus appeared to be the most epileptogenic site tested because hippocampal iron deposition that did not include the dentate gyrus, or iron deposition in the entorhinal cortex, was significantly less epileptogenic.

Animals↗

PubMed1993

Intrinsic properties and evoked responses of guinea pig subicular neurons in vitro.

1. Intracellular recordings were used to examine the membrane properties and evoked responses of subicular neurons in horizontal and parasagittal slices from guinea pig brain as a step toward understanding excitatory transmission through the hippocampus. 2. Most cells (49/74) could fire a burst discharge, a portion of which was Ca2+ dependent, in response to direct depolarization or in response to orthodromic or antidromic activation. Other cells (23/74) could not be made to burst, but instead fired single repetitive spikes when directly depolarized or single spikes in response to orthodromic or antidromic activation. Two recorded cells appeared to be interneurons and differed from bursting and non-bursting cells in action-potential shape and response to extracellular stimulation. 3. Bursting cells differed from nonbursting cells in their membrane properties: 1) their time constants were typically shorter (averaging 7.4 ms for bursting cells and 11.5 ms for nonbursting cells), 2) they exhibited a pronounced "sag" in the potential response to hyperpolarizing current injection, and 3) they responded at the break of a hyperpolarizing stimulus with a depolarization (anodal break potential). The sag and the anodal break potential were not detected in recordings from nonbursting neurons. 4. A single-spiking mode could be induced in bursting cells by depolarization from resting potential to about -60 mV. Conversely, hyperpolarization of nonbursting cells did not convert them to bursting cells. 5. Both bursting and nonbursting cell types could be antidromically driven. Whereas both excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) were prominent in nonbursting cells, IPSPs were observed at a lower stimulus intensities than EPSPs in most cells. EPSPs were evident in bursting cells and they triggered burst discharges. IPSPs in bursting cells were detected only when these cells were depolarized, eliminating burst responses. 6. Spontaneous firing rates were low (averaging < 1 spike/s) for both cell types. Addition of picrotoxin produced spontaneous burst or EPSP responses in bursting cells, synchronous with different patterns of picrotoxin-induced population bursts originating in CA3 and/or entorhinal cortex. Individual subicular cells followed CA3 or entorhinal cortex or both. No such activity was recorded in nonbursting cells. No increases in activity in either cell type were seen after picrotoxin application to isolated pieces of subicular cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1999

Distribution of GABAergic cells and fibers in the hippocampal formation of the macaque monkey: an immunohistochemical and in situ hybridization study.

The gamma-aminobutyric acid (GABAergic) system of the hippocampal formation of Macaca fascicularis monkeys was studied immunohistochemically with a monoclonal antibody to GABA and with nonisotopic in situ hybridization with cRNA probes for glutamic acid decarboxylase 65 (GAD65) and GAD67. The highest densities of labeled cells were observed in the presubiculum, parasubiculum, entorhinal cortex, and subiculum, whereas the CA3 field and the dentate gyrus had the lowest densities of positive neurons. Within the dentate gyrus, most of the GABAergic neurons were located in the polymorphic layer and in the deep portion of the granule cell layer. GABAergic terminals were densest in the outer two-thirds of the molecular layer. GABAergic neurons were seen throughout all layers of the hippocampus. Terminal labeling was highest in the stratum lacunosum-moleculare. A higher terminal labeling was observed in the subiculum than in CA1 and was particularly prominent in layer II of the presubiculum. A bundle of GABAergic fibers was visible deep to the cell layers of the presubiculum and subiculum. This bundle could be followed into the angular bundle ipsilaterally and was continuous with stained fibers in the dorsal hippocampal commissure. This pattern of labeling is reminiscent of the presubicular projections to the contralateral entorhinal cortex. GABAergic cells were observed in all layers of the entorhinal cortex although the density was higher in layers II and III than in layers V and VI. The in situ hybridization preparations largely confirmed the distribution of GABAergic neurons in all fields of the hippocampal formation.

Animals↗

PubMed1993

Temporal lobe atrophy on magnetic resonance imaging in the diagnosis of early Alzheimer's disease.

OBJECTIVE: To evaluate the use of simple ratings and linear measures of atrophy in the temporal lobe structures obtained with magnetic resonance imaging coronal scans in the diagnosis of early Alzheimer's disease. DESIGN: Prospective series. The National Institute for Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease. Blinded assessment. SETTING: Dementia study in a university hospital. SUBJECTS: Patients with Alzheimer's disease (n = 34), scoring 150 or more on the Extended Scale for Dementia, and age-matched healthy community volunteers (n = 39) who had both magnetic resonance imaging coronal scans and a psychometric assessment using the Extended Scale for Dementia within 6 months were included. MEASURES MAIN MEASURES: T1-weighted magnetic resonance imaging coronal scans, a 1.5-T system. The degree of atrophy rated (0 to 4) in both sides of the temporal neocortex, entorhinal cortex, hippocampal formation, temporal horns, third ventricle, lateral ventricles, and frontal and parietal cortex. Linear measures: the area of hippocampus and the maximal transverse width of temporal horns. RESULTS: Differentiation between patients with Alzheimer's disease and controls was limited by considerable variations in sensitivity and specificity. Receiver operating characteristics analysis revealed a clear order of discrimination, the entorhinal cortex and the temporal neocortex being the two best, followed by the temporal horns and hippocampal formation. For a given specificity of 90%, the corresponding sensitivity for the entorhinal cortex, temporal neocortex, temporal horns, and hippocampal formation was 95%, 63%, 56%, and 41%, respectively. Linear measures differed significantly but showed considerable overlap. CONCLUSION: The presence of rated atrophy in selected temporal structures makes the diagnosis of Alzheimer's disease more likely, but the absence does not rule out the possibility of early Alzheimer's disease.

Adult↗

PubMed1990

Tyrosine hydroxylase-immunoreactive neurons in the temporal lobe in complex partial seizures.

The anterior mesial portion of the temporal lobe removed from 16 patients who underwent surgery for the treatment of complex partial seizures was found to contain tyrosine hydroxylase-immunoreactive neurons. The distribution of these neurons was correlated with the underlying neuropathological features. Ammon's horn sclerosis was present in 8 patients; a ganglioglioma, in 7 patients; and an infarction in the distribution of the middle cerebral artery, in 1 patient. Tyrosine hydroxylase-immunoreactive neurons were found in Ammon's horn of 6 of the 8 patients with Ammon's horn sclerosis, and in the subiculum and entorhinal cortex of all 8 patients with the same pathology. None of these neurons were found in Ammon's horn of the 7 patients with a ganglioglioma, but were found in the subiculum of 5 of the 7 patients and in entorhinal cortex of all 7 patients. Tyrosine hydroxylase immunoreactivity was also studied in 13 control autopsy specimens. No tyrosine hydroxylase-immunoreactive neurons were found in Ammon's horn or the subiculum of any of the control specimens, but were found in the entorhinal cortex of 6 of the 13 specimens. The tyrosine hydroxylase-immunoreactive neurons in the mesial portion of the temporal lobe of patients with complex partial seizures may contribute to the increased levels of tyrosine hydroxylase found in neurochemical studies of specimens taken at temporal lobectomy.

Adolescent↗

PubMed1987

Hippocampal electrical activity following local tetanization. I. Afterdischarges.

Following a short (1-10 s) train of repetitive stimulation delivered to the hippocampal CA1 region, the following sequelae of afterdischarges (ADs) was seen: (1) a silent period of 2-4 s, (2) a large primary (1 degree) AD usually alvear-surface negative and deep positive, (3) a period of suppressed hippocampal EEG, (4) a secondary (2 degrees) hippocampal AD, and after 3-6 min, (5) 15-25 min of enhanced (up to 10 times normal) fast (30-70 Hz) waves. The 2 degrees hippocampal AD was preceded by or simultaneous with large AD at the amygdaloid electrodes. Electrolytic lesions (n = 7) or large heat lesions of the amygdala (n = 5) or electrolytic lesions of the medial septum (n = 10) were not successful in suppressing the 2 degrees hippocampal AD. However, 4 rats with radiofrequency lesion and 3 rats with bilateral aspiration lesion of the entorhinal cortex had diminished or no 2 degrees hippocampal AD. The fast waves after tetanization were reversed 180 degrees across surface and deep CA1 electrodes. The fast wave increase was blocked by atropine sulfate (25-50 mg/kg i.p.), scopolamine hydrochloride (5 mg/kg i.p.) and medial septal lesions. It was concluded that the 2 degrees hippocampal AD may depend on a reverberation of neural circuitry involving the entorhinal cortex. The 2 degrees AD recorded from amygdala electrodes may partly reflect spreading of activities from the entorhinal cortex. On the other hand, the increase in fast waves after tetanization requires an intact septohippocampal, muscarinic cholinergic input, and may depend on an enhanced cholinergic input or an increased response.

Action Potentials↗

PubMed1991

Morphological characterization of rat entorhinal neurons in vivo: soma-dendritic structure and axonal domains.

We used in vivo intracellular labeling with horseradish peroxidase in order to study the soma-dendritic morphology and axonal projections of rat entorhinal neurons. The cells responded to hippocampal stimulation with inhibitory postsynaptic potentials, and thus likely received direct or indirect hippocampal input. All cells (n = 24) showed extensive dendritic domains that extended in some cases for more than 1 mm. The dendrites of layer II neurons were largely restricted to layers I and II or layers I-III, while the dendrites of deeper cells could extend through all cortical layers. Computed 3D rotations showed that the basilar dendrites of deep pyramids extended roughly parallel to the cortical layering, and that they were mostly confined to the layer containing the soma and layers immediately adjacent. Total dendritic lengths averaged 9.8 mm +/- 3.8 (SD), and ranged from 5 mm to more than 18 mm. Axonal processes could be visualized in 21 cells. Most of these showed axonal branching within the entorhinal cortex, sometimes extensive. Efferent axonal domains were reconstructed in detail in 3 layer II stellate cells. All 3 projected axons across the subicular complex to the dentate gyrus. One of these cells showed an extensive net-like axonal domain that also projected to several other structures, including the hippocampus proper, subicular complex, and the amygdalo-piriform transition area. The axons of layer III and IV cells projected to the angular bundle, where they continued in a rostral direction. In contrast to the layer II, III and IV cells, no efferent axonal branches leaving the entorhinal cortex could be visualized in 5 layer V neurons. The data indicate that entorhinal neurons can integrate input from a considerable volume of entorhinal cortex by virtue of their extensive dendritic domains, and provide a further basis for specifying the layers in which cells receive synaptic input. The extensive axonal branching pattern seen in most of the cells would support divergent propagation of their activity.

Animals↗

PubMed2006

Impairment of odor recognition in Parkinson's disease caused by weak activations of the orbitofrontal cortex.

Olfactory dysfunction and abnormalities of olfactory brain structures are found in patients with Parkinson's disease (PD), and a number of studies have reported that olfactory dysfunction is caused by abnormalities of the central olfactory systems. We previously analyzed electroencephalograms (EEGs) and respiration simultaneously in normal subjects while testing for detection and recognition of odors. We identified changes in respiration pattern in response to odor stimuli and found inspiratory phase-locked alpha oscillations (I-alpha). The genesis of I-alpha were identified in olfactory-related areas including the entorhinal cortex, hippocampus, amygdale and orbitofrontal cortex with an EEG dipole tracing method. In the present study, we used the same protocol in PD patients and compared results of PD with those of age-matched controls. All PD patients detected odor, but 5 out of 10 showed impaired odor recognition. Changes in breathing pattern associated with emotional changes during exposure to odor stimuli were not observed in PD patients. I-alpha waveforms were not observed; however, positive waves followed by negative waves were identified approximately 100ms after inspiration onset. Dipoles of this component were localized in the entorhinal cortex for odor detection in all patients and in the entorhinal cortex and middle temporal gyrus for PD patients who could discriminate odors. Odor recognition in PD could be subserved by a different neural circuit from that of normal subjects, done through the temporal association cortex as a subsystem for recognizing the odor; however, the system may not be associated with the odor-induced emotions.

Aged↗

PubMed1991

Mechanism of electrographic seizure generation in the rat brain slice in low magnesium medium: modulatory effect of interictal bursting on seizure generation.

In order to understand the mechanisms underlying seizure generation, the present study investigated the functional and anatomical interaction between seizures and interictal bursts. Bathing rat brain slices of the hippocampus and entorhinal cortex in zero magnesium medium elicited electrographic seizures. In the later period, the electrographic seizures were eventually replaced by the interictal bursts. In this phase, lowering [K+]o and raising [Ca2+]o restored the tonic seizures by suppressing the interictal bursts. A multiple knife cut experiment revealed that the seizures arose in the entorhinal cortex and the interictal bursts originated in CA3. A selective knife cut across the subiculum showed that the interictal bursts, propagating from CA3 to the entorhinal cortex, disrupted and suppressed the electrographic seizures in standard Mg(2+)-free medium.

Animals↗

PubMed1986

Distribution of altered hippocampal neurons and axons immunoreactive with antisera against neuropeptide Y in Alzheimer's-type dementia.

This paper provides detailed information on the distribution of neuropeptide tyrosine (neuropeptide Y; NPY) immunoreactive neurons and fibers in the hippocampal region of eight neuropathologically confirmed cases of Alzheimer's-type dementia (ATD) at postmortem. These neuronal networks are detected by a polyclonal antibody raised against the unconjugated peptide and controls were obtained by using liquid phase absorption immunocytochemistry. The description covers the subfields area dentata, CA3 and CA1, the subicular complex, and the entorhinal area. The hippocampal regions in which the NPY-i neuron networks are most severely affected are the hilus, CA1, the parasubiculum, and the entorhinal cortex. Less obvious reductions occurred in CA3, subiculum, and the presubiculum. Parallel semiquantitative estimates were made of the numbers of neuritic plaques and neurofibrillary tangles in the other hippocampus of the brains in every ATD case. The areas of heaviest pathological changes by these indices are CA1 and the entorhinal cortex. The subicular complex CA3 and the area dentata are less affected. These findings show that the areas with the most severe loss of NPY-i neurons and axons, CA1 and the entorhinal cortex, are the same as those areas most severely affected by the other indices of ATD. Thus NPY-i networks are involved in the ATD disease process. However, other NPY-i networks survive, in some subfields better than in others. The cumulative evidence suggests a population of hippocampal peptide neurons that are remarkably resistant in terminal neurological disease. These neurons have the capability to participate in the maintenance of minimal functioning circuits in target areas of the disease and as such hold significant links for our understanding of synaptic plasticity in disease.

Aged↗

PubMed1997

Nicotinic and muscarinic cholinergic receptor binding in the human hippocampal formation during development and aging.

High-affinity nicotine, alpha-bungarotoxin (alpha BT) and muscarinic receptor binding was measured in the human hippocampal formation in a series of 57 cases aged between 24 weeks gestation and 100 years. Changes in nicotine receptor binding during development and aging were more striking than differences in alpha BT and muscarinic binding. Nicotine binding was higher at the late foetal stage than at any other subsequent time in all areas investigated. In the hippocampus a fall in binding then occurred within the first six months of life, with little or no subsequent fall during aging, whereas in the entorhinal cortex and the presubiculum the major loss of nicotine binding occurred after the fourth decade. alpha BT binding was significantly elevated in the CA 1 region, but in no other region of the hippocampus, in the late foetus, and there was also a fall in alpha BT binding in the entorhinal cortex during aging from the second decade. The modest changes in total muscarinic binding, which appeared to reflect those in M1 and M3 + 4 rather than M2 binding, were a rise in the entorhinal cortex between the foetal stage and childhood and a tendency for receptors to fall with age in the hippocampus and subicular complex. These findings implicate mechanisms controlling the expression of nicotinic receptors to a greater extent than muscarinic receptors in postnatal development and aging in the human hippocampus.

Adolescent↗

PubMed1994

Regional and temporal pattern of expression of nerve growth factor and basic fibroblast growth factor mRNA in rat brain following electroconvulsive shock.

We have previously reported that focally evoked limbic motor seizures rapidly increase levels of mRNA encoding nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) in specific limbic system areas of the adult rat brain. The present studies examined the effect of both minimal and maximal electroconvulsive shock, applied via corneal electrodes, on NGF and bFGF mRNA levels in several limbic (entorhinal cortex, hippocampus, olfactory bulb) and extralimbic (striatum and cerebellum) brain regions. By 5 h following limbic motor seizures induced by low-intensity (minimal) electroshock (LES) (0.2 s, 50-70 mA; three times over a 1-h period), bFGF mRNA was significantly increased in entorhinal cortex and hippocampus, but not in the other regions examined. In contrast, tonic extensor seizures evoked by maximal electroshock (MES) (0.2 s, 150 mA; three times over a 1-h period) were associated with a significant increase in bFGF mRNA in all limbic and extralimbic regions examined. In the same animals, increases in NGF mRNA were limited to entorhinal cortex and hippocampus. Adrenal steroids were not required for the seizure-induced increase in NGF or bFGF mRNAs, based on the finding that adrenalectomized rats exhibited electroshock-induced increases in both NGF and bFGF mRNAs equivalent to the increase observed in sham-operated rats. It is suggested that the increase in mRNA levels for the neurotrophic factors occurs selectively in those regions which are especially activated by the specific seizure model, and represents an adaptive response to repeated noninjurious neuronal stimulation.

Adrenalectomy↗

PubMed1988

Ultrastructural characterization of the synapses of the crossed temporodentate pathway in rats.

The present study was undertaken to define the ultrastructure of synapses of the crossed temporodentate pathway from the entorhinal cortex to the contralateral dentate gyrus and to compare the synapses of the sparse crossed pathway with those of the massive ipsilateral temporodentate pathway. The synapses of the crossed pathway were identified by using EM degeneration and EM autoradiographic techniques. For the degeneration studies, adult male Sprague-Dawley rats were killed 1, 2, or 4 days following a unilateral entorhinal cortex lesion and prepared for electron microscopy. To identify the synapses by using autoradiographic techniques, four animals received injections of 3H-proline into the entorhinal cortex, were allowed to survive for 3 days, and were prepared for EM autoradiography. Degenerating synapses of the crossed pathway that were found in the molecular layer of the dentate gyrus contralateral to a lesion formed asymmetric synapses on spines and possessed presynaptic organelles indistinguishable from synapses of the ipsilateral temporodentate pathway. The number of degenerating synapses was very low at all survival intervals (14.80 degenerating synapses/10,000 microns2 at 1 day postlesion and 1.95 degenerating synapses/10,000 microns2 at 2 days postlesion); no degenerating synapses were found at 4 days postlesion. Ninety-eight percent of the degenerating synapses found at 1 day postlesion exhibited electron-lucent degeneration. At 2 days postlesion 83% of the degenerating synapses in the dorsal blade and 18% of those in the ventral blade showed lucent degeneration; the remainder were electron dense. EM autoradiography confirmed the degeneration studies in terms of the type of terminals that were labeled and suggested that the density of the crossed pathway was higher than the degeneration results implied. We conclude that synapses of the crossed temporodentate pathway have a similar ultrastructure to synapses of the ipsilateral temporodentate pathway but exhibit a rapid form of degeneration such that they disappear very rapidly following the lesion.

Animals↗

PubMed1993

Continuity of neuropil threads with tangle-bearing and tangle-free neurons in Alzheimer disease cortex. A confocal laser scanning microscopy study.

Neuropil threads (NTs) are abnormal processes that are associated with tangle-bearing neurons in gray matter areas of Alzheimer disease (AD) brains. Although NTs contain paired helical filaments (PHFs) and share multiple tau epitopes with neurobrillary tangles (NFTs), the relationship between NTs and tangle-bearing neurons is unclear. For this reason, we assessed the continuity of NTs with tangle-bearing and tangle-free neurons. Since astrocytes express low levels of tau and rarely have been shown to contain PHFs, we also examined the relationship of NTs to cortical astrocytes. This was done using histochemical and immunochemical methods in conjunction with confocal laser scanning microscopy to examine NTs in amygdala and entorhinal cortex of seven AD brains. Only a small fraction of NTs (< 1%) in 3.5 x 10(6) microns 3 of amygdala and entorhinal cortex could be traced to local neurons with NFTs or to neurons that did not contain NFTs, and no NTs were continuous with cortical astrocytes. These results indicate that only a very small percentage of NTs in entorhinal cortex and amygdala occur in the most proximal segments of processes that emanate from tangle-bearing or tangle-free neurons. This implies that the majority of NTs reside in the distal parts of dendrites and/or the terminal arborizations of axons or that NTs are discontinuous abnormalities. Taken together, these data suggest that NTs could disrupt local and long distance neuronal circuitry and thereby contribute to the cognitive impairments seen in AD patients.

Aged↗

PubMed2003

MRI-guided SPECT perfusion measures and volumetric MRI in prodromal Alzheimer disease.

OBJECTIVE: To identify group differences in the prodromal phase of Alzheimer disease (AD) using quantitative single-photon emission computed tomography (SPECT) perfusion and magnetic resonance imaging (MRI) volume measures within specific volumes of interest. SETTING: Gerontology research unit. PARTICIPANTS: There were 17 healthy controls, 56 nondemented patients with memory problems who did not develop AD during 3 to 5 years of follow-up (questionables), and 27 nondemented patients with memory problems who developed AD during follow-up (converters). METHODS: A Tc 99m hexamethylpropyleneamine oxime SPECT study and an MRI were performed in each participant at baseline. Mean SPECT activity concentration and MRI volume were estimated within 9 structures: rostral anterior cingulate, caudal anterior cingulate, posterior cingulate, hippocampus, entorhinal cortex, basal forebrain, temporal horn, amygdala, and the banks of the superior temporal sulcus. Data were analyzed using overall and pairwise discriminant analysis, and performance in pairwise group discrimination was measured using correlated receiver operating characteristic curve analysis. RESULTS: The overall (3-group) discriminant function was significant for SPECT (F test, P<.001) and MRI (F test, P<.0001). For the SPECT analysis, the ranking of structures for discriminating among the 3 groups was, in order of decreasing discriminating power, caudal anterior cingulate, temporal horn, superior temporal sulcus, entorhinal cortex, hippocampus, rostral anterior cingulate, amygdala, basal forebrain, and posterior cingulate. For the MRI analysis, this ranking was entorhinal cortex, superior temporal sulcus, temporal horn, hippocampus, amygdala, caudal anterior cingulate, rostral anterior cingulate, basal forebrain, and posterior cingulate. Combining the 2 modalities yielded significantly better discrimination performance than did either alone. Furthermore, the correlation between SPECT and MRI measures was low. CONCLUSION: Measures of structure activity concentration and volume carry independent information; both reveal group differences in prodromal AD.

Aged↗

PubMed2003

Mesial temporal damage in temporal lobe epilepsy: a volumetric MRI study of the hippocampus, amygdala and parahippocampal region.

Despite neuropathological and electrophysiological evidence for the involvement of parahippocampal structures in temporal lobe epilepsy (TLE), little attention has been paid to morphometric measurements of these structures in patients with TLE. Using high resolution MRI, we previously showed that the volume of the entorhinal cortex was decreased in patients with TLE. The purpose of this study was: (i) to determine whether changes in the volume of the perirhinal cortex and posterior parahippocampal cortex were detectable by MRI; and (ii) to study the distribution and degree of atrophy in mesial temporal structures including the hippocampal head, body and tail, amygdala, entorhinal cortex, perirhinal cortex and posterior parahippocampal cortex. MRI volumetric analysis was performed using a T(1)-weighted three-dimensional gradient echo sequence in 20 healthy subjects and 25 TLE patients with intractable TLE. In patients with either left or right TLE, the hippocampal head, body and tail and the entorhinal and perirhinal cortices ipsilateral to the seizure focus were significantly smaller than in normal controls. The mean volume of the posterior parahippocampal cortex was not different from that of normal controls. Within the hippocampus, the hippocampal head was more atrophic than the hippocampal body and hippocampal tail. Within the parahippocampal region, the entorhinal cortex was more severely affected than the perirhinal cortex. Our MRI results confirm pathological findings of damage in the mesial temporal lobe, involving not only the hippocampus and the amygdala, but also the entorhinal and perirhinal cortices. The pattern of atrophy may be explained by cell loss secondary to a disruption of entorhinal-hippocampal connections as a result of privileged electrical dialogue between these two structures.

Adolescent↗

PubMed2000

Sodium bromide: effects on different patterns of epileptiform activity, extracellular pH changes and GABAergic inhibition.

Results regarding the anticonvulsant potency of bromide have been questioned, and the mechanisms of its action are unclear. Using combined rat hippocampus-entorhinal cortex slices we analyzed the effects of NaBr on four types of epileptiform discharges in two different models of epilepsy, the low-Ca2+ and the low-Mg2+ model. NaBr concentration-dependently reduced the frequency and finally blocked the low Ca2+-induced discharges. Low Mg2+-induced short recurrent discharges were also reduced in a concentration-dependent manner. In the entorhinal cortex the frequency of seizure-like events was reduced by 3 and 5 mM and the discharges were blocked by 7 mM NaBr. Also, the late recurrent discharges in the entorhinal cortex which do not respond to most clinically employed anticonvulsants were reduced by concentrations of 10 and 15 mM and completely blocked by 30 mM NaBr. Using pH-sensitive microelectrodes different effects of NaBr were seen than those of acetazolamide on extracellular pH under control conditions and after stimulation. Acetazolamide at 1 mM caused a reversible acidification of delta pH: 0.2+/-0.14 at rest whereas no change on extracellular pH was seen with 5 mM NaBr. Acetazolamide increased the transient alkalosis induced by repetitive stimulation of the stratum radiatum in area CA1 and reduced the subsequent acidosis. NaBr also increased the alkalosis but had no effect on the subsequent acidosis. A significant increase in paired-pulse inhibition was seen in a paired-pulse stimulation protocol used to monitor the efficacy of GABAergic inhibition at concentrations of 5 mM NaBr. This finding was confirmed in whole-cell patch clamp recordings from cultured hippocampal neurons showing an increase in inhibitory postsynaptic current amplitude. In summary, our results suggest a broad-spectrum anticonvulsant activity which is likely to be caused by its effects on membrane excitability, by an increase in GABAergic inhibition and is less likely caused by its effects on extracellular pH.

Acetazolamide↗