Search PubMed⌕ Search

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.

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

At least 1,135 records · Page 63Linked to original sources
PubMed1998

Selective deposition of amyloid-beta protein in the entorhinal-dentate projection of a transgenic mouse model of Alzheimer's disease.

Early and selective deposition of amyloid beta protein(Abeta) is thought to be a pathological feature central to Alzheimer's disease (AD). It has been a great challenge to identify the mechanism(s) responsible for the selectivity of Abeta deposition and the deposition into a temporal sequence of the pathogenesis in this disorder. We now report that the transgenic mouse (PDAPP), which overexpresses the human amyloid precursor protein containing the familial AD mutation (APP717V-F), develops brain region-specific Abeta deposits along with some pathologies associated with AD. By using monoclonal antibodies that recognize multiple sites on the human Abeta peptide, we show that Abeta deposits are localized primarily to the entorhinal cortex and hippocampal/dentate gyrus regions. Abeta deposition exhibited consistent laminar distribution throughout the hippocampal formation that was confined mostly to a dense terminal field in the outer portion of the stratum moleculare of the dentate gyrus and the stratum lacunosum of the hippocampus proper of 13-month-old heterozygous PDAPP mice. Abeta deposits were also observed in the supragranular zone of the dentate gyrus. Similarly, laminar distribution of Abeta deposits were evident in the entorhinal cortex, most notably in the molecular layer and in laminar layer II-III. The defined laminar pattern of the Abeta deposition, which resembles that of AD, suggests that intrinsic factors in the perforant path, the major projection from the entorhinal cortex to the hippocampal formation, and their respective local paths contribute, at least in part, to the extracellular Abeta deposition in the transgenic mouse model of AD.

Alzheimer Disease↗
PubMed1998

Expression of the alpha3 nicotinic receptor subunit mRNA in aging and Alzheimer's disease.

Changes in the number of high-affinity nicotine binding sites have been widely reported in specific regions of the human brain during aging and in degenerative neurological diseases associated with aging, such as Alzheimer's disease. Nicotinic receptors are highly diverse and a description of the molecular subtypes affected in such conditions has not been achieved to date. To investigate the status of the alpha3 subunit-containing subtypes in such conditions, we assessed by in situ hybridisation the alpha3 mRNA density in the hippocampus, entorhinal cortex and thalamus of Alzheimer's patients and age-matched controls. No significant difference in the expression of the alpha3 mRNA, either qualitative or quantitative, was found between Alzheimer's individuals and controls in any of the analysed areas. This result suggests that the nicotine binding changes occurring in these areas in Alzheimer's patients are not correlated to a variation of the alpha3 mRNA in the same regions. Nevertheless, a negative correlation between the alpha3 mRNA density and the age was observed in the entorhinal cortex of both the Alzheimer's and the normal subjects, suggesting a potentially extensive decay of the alpha3-expressing neurons or loss of alpha3-containing receptors in intact neurons of the entorhinal cortex in the late elderly.

Aged↗
PubMed2003

Testosterone, but not nonaromatizable dihydrotestosterone, improves working memory and alters nerve growth factor levels in aged male rats.

Recent studies have suggested that testosterone levels are lower in men with Alzheimer's disease and that testosterone treatment improves cognition in older men. Since testosterone can be aromatized to estrogen, testosterone's effects could be due to conversion into estrogen. We treated aged male rats with either testosterone or dihydrotestosterone (DHT), the latter of which is not aromatized to estrogen, in order to determine whether these treatments improve spatial working and reference memory as assessed in the water radial arm maze. We also tested whether such effects are related to beta-amyloid levels in the hippocampus or neurotrophin levels in the hippocampus, entorhinal cortex, frontal cortex, or striatum. Aged rats made more errors than young rats on all memory measures. Testosterone, but not DHT, improved working memory and decreased hippocampal NGF protein in aged rats, while having no effect on beta-amyloid. However, higher beta-amyloid levels were correlated with poorer working memory performance in young rats. Neurotrophin levels in entorhinal cortex were positively correlated with errors for all memory measures in androgen-treated rats. Similar to findings in human studies, in our study androgen treatment lowered circulating estradiol levels in aged rats, suggesting that androgen treatment exerts feedback to the hypothalamic pituitary axis and that conversion to estrogen may not be the underlying biological mechanism of testosterone's effects on memory and growth factor levels. The ratio of estradiol to testosterone, or the actions of the aromatase enzyme itself, may be responsible for the observed effects. These data support the hypothesis that testosterone therapy in aging men may provide positive effects on cognition and that neural regions that are linked to cognition, such as the hippocampus and/or entorhinal cortex, may be involved in such effects.

Aging↗
PubMed2001

MR volumetry of the entorhinal, perirhinal, and temporopolar cortices in drug-refractory temporal lobe epilepsy.

BACKGROUND AND PURPOSE: The occurrence of damage in the entorhinal, perirhinal, and temporopolar cortices in unilateral drug-refractory temporal lobe epilepsy (TLE) was investigated with quantitative MR imaging. METHODS: Volumes of the entorhinal, perirhinal, and temporopolar cortices were measured in 27 patients with unilateral drug-refractory TLE, 10 patients with extratemporal partial epilepsy, and 20 healthy control subjects. All patients with TLE were evaluated for epilepsy surgery and underwent operations. RESULTS: In left TLE, the mean volume of the ipsilateral entorhinal cortex was reduced by 17% (P <.001 compared with control subjects) and that of the ipsilateral temporopolar cortex by 17% (P <.05). In right TLE, the mean ipsilateral entorhinal volume was reduced by 13% (P < or =.01), but only in patients with hippocampal atrophy. Asymmetry ratios also indicated ipsilateral cortical atrophy. When each patient was analyzed individually, the volume of the ipsilateral hippocampus was reduced (> or = 2 SD from the mean of controls) in 63% and that of the entorhinal cortex in 52% of patients with TLE. Furthermore, ipsilateral entorhinal (left: r = 0.625, P <.001; right: r = 0.524, P < or =.01), perirhinal (left: r = 0.471, P <.05), and temporopolar (right: r = 0.556, P <.01) volumes correlated with ipsilateral hippocampal volumes. There was no association, however, with clinically or pathologically identified causes of epilepsy, duration of epilepsy, or age at onset of epilepsy. Mean cortical volumes were unaffected in extratemporal partial epilepsy. CONCLUSION: Subpopulations of patients with unilateral TLE have ipsilateral damage in the entorhinal and temporopolar cortices. The damage is associated with hippocampal damage.

Adolescent↗
PubMed1984

Laminar origin and septotemporal distribution of entorhinal and perirhinal projections to the hippocampus in the cat.

The projections of the entorhinal and perirhinal cortices to the hippocampus in the cat have been studied with retrograde and anterograde tracing techniques. Retrogradely transported tracers, which were injected at different levels along the septotemporal longitudinal hippocampal axis, result in labeled neurons in superficial entorhinal cortical layers II and III. Occasionally, labeled cells were also observed in the deepest entorhinal layer as well as in the superficial layers of the perirhinal area 35. It could further be shown that labeled neurons located superficially in the entorhinal cortex are topographically distributed in a lateromedial gradient, which corresponds to a septotemporal gradient along the longitudinal axis of the hippocampus. This topographical organization of the entorhinal-hippocampal projection system could be substantiated by the use of anterograde tracing of radioactively labeled amino acids. Injections in the entorhinal cortex produce labeled fibers in the hippocampus. Injections in the perirhinal area 35 result also in labeling over the hippocampus, whereas area 36 does not seem to distribute fibers to the hippocampus. As anticipated from the results of the retrograde tracing experiments, injections located laterally, in or close to the posterior rhinal sulcus, produce prominent labeling over the septal pole of the hippocampus, whereas progressively more medially located injections result in progressively more temporally located labeling. This topographical distribution of perforant path fibers along the septotemporal axis of the hippocampus, which is related to a lateromedial axis in the entorhinal cortex, has been observed following injections in the lateral entorhinal area (LEA) as well as in the medial entorhinal area (MEA). The present observations are discussed in regard of other connectional and putative functional differences between the septal and temporal hippocampus.

Animals↗
PubMed2000

Anatomical organization of the parahippocampal-hippocampal network.

The anatomical organization of the parahippocampal-hippocampal network indicates that it consists of different parallel circuits. Considering the topographical distribution of sensory cortical inputs, the hypothesis is that the major parallel circuits carry functionally different information. These functionally different parallel routes reach different portions of the hippocampal network along the longitudinal axis of all fields as well as along the perpendicularly oriented transverse axis of CA1 and the subiculum. In the remaining fields of the hippocampal formation, that is, the dentate gyrus and CA2/CA3, separation along the transverse axis is not present. By contrast, here the functionally different pathways converge onto the same neuronal population. The entorhinal cortex holds a pivotal position among the cortices that make up the parahippocampal region. By way of the networks of the superficial and deep layers, it mediates, respectively, the input and output streams of the hippocampal formation. Moreover, the intrinsic entorhinal network, particularly the interconnections between the deep and superficial layers, may mediate the comparison of hippocampal input and output signals. As such, the entorhinal cortex may form part of a novelty detection network. In addition, the organization of the entorhinal-hippocampal network may facilitate the holding of information. Finally, the terminal organization of the presubicular input to the medial entorhinal cortex indicates that the interactions between the deep and superficial entorhinal layers may be influenced by this input.

Animals↗
PubMed1992

Reverberatory seizure discharges in hippocampal-parahippocampal circuits.

Previously, a unique type of epileptiform discharge, recorded in the dentate gyrus, has been identified and termed maximal dentate activation. Maximal dentate activation is defined by the presence of bursts of large amplitude population spikes, associated with a secondary rise in the extracellular potassium and a negative shift of the dc potential. Prior work has linked maximal dentate activation to lengthening of afterdischarges when they are elicited in the hippocampus or outside of the hippocampus in the amygdala. The current study used two approaches to further examine the relationship of maximal dentate activation to seizures in limbic circuits in urethane-anesthetized rats. First, simultaneous recordings were employed to document that during maximal dentate activation, synchronous discharges occurred in the dentate gyrus, cornu Ammonis, subiculum, and entorhinal cortex. From anatomical work, these structures are known to be connected in a hippocampal-parahippocampal loop. The second approach used lesions of the entorhinal cortex to document the importance of this loop in the initiation and maintenance of maximal dentate activation. Both electrolytic and chemical (focal injections of tetrodotoxin) lesions of the entorhinal cortex blocked maximal dentate activation on the side of the lesion. However, maximal dentate activation was maintained on the opposite side, where the hippocampal-parahippocampal loop was intact. Altogether, these data support the hypothesis that maximal dentate activation is a marker for the presence of reverberatory, synchronized paroxysmal activity throughout the hippocampal-parahippocampal loop and that this loop behaves as a unit in epileptogenesis.

Animals↗
PubMedDate not supplied

Expression of neurotrophins BDNF and NT-3, and their receptors in rat brain after administration of antipsychotic and psychotrophic agents.

We have investigated the potential role of neurotrophic factors in antipsychotic drug action by examining the effects of antipsychotic and psychotropic treatments on the mRNA expression of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and their receptors, trkB and trkC, respectively, in rat brain. Neither acute nor chronic clozapine treatment significantly affected the expression of these mRNAs in any brain area investigated, except for a decrease in trkB expression in the granule cells of the olfactory bulb. We then examined the effects of the psychotropic agent MK-801. MK-801 (5 mg/kg; 4 h) significantly increased BDNF mRNA in the entorhinal cortex, but did not influence NT-3, trkB, or trkC expression in any brain area except for the olfactory bulb. The induction of BDNF mRNA by MK-801 was attenuated by pre-treatment (1 h prior to MK-801 administration) with the antipsychotics, clozapine (25 mg/kg) and haloperidol (2 mg/kg), but not with the antidepressant desipramine (15 mg/kg). Finally, we confirmed that the effects of MK-801 on BDNF mRNA were reflected in the respective changes in BDNF protein levels: MK-801 significantly increased anti-BDNF reactivity in the entorhinal cortex (126 +/- 7% of control) while concomitantly decreasing in the hippocampus (71 +/- 2% of control). These data do not support the hypothesis that neurotrophins play an important role in antipsychotic drug action, but rather suggest that induction of BDNF in the entorhinal cortex may play a significant role in the psychotropic action of MK-801.

Animals↗
PubMed1997

Temporal lobe magnetic resonance imaging can differentiate Alzheimer's disease from normal ageing, depression, vascular dementia and other causes of cognitive impairment.

BACKGROUND: Previous work suggests that temporal lobe magnetic resonance imaging (MRI) can distinguish those with dementia of the Alzheimer type (DAT) from healthy age-matched controls. However, its specificity with regard to conditions such as vascular dementia, depression and other disorders associated with cognitive impairment has not been determined. METHODS: We studied 222 subjects using T1 weighted MRI with 5.1 mm coronal slices throughout the temporal lobe. Subjects included: healthy controls (N = 40); DSM-III-R major depression (N = 61); NINCDS/ADRDA DAT (N = 77) and OTHER (N = 44, comprising subjects with vascular dementia, Huntington's disease, schizophrenia, alcohol related cognitive impairment and a group of 'memory complainers'). Hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus and cerebral cortex were rated visually on a 0-3 scale by two experienced neuroradiologists blind to clinical diagnosis. RESULTS: Ratings of temporal lobe atrophy provided good separation between those with AD and all other groups. For example, anterior hippocampal atrophy had a sensitivity of 83% for detecting DAT, a specificity of 80% for controls, 87% for depressed subjects and 89% for OTHER. Other regions were less sensitive, but more specific for the diagnosis of DAT. In particular parahippocampal gyrus and entorhinal cortex had high specificity (97% for depressed subjects and 98% for OTHER). Because of an age-related increase in atrophy, sensitivity was highest for those over the age of 75, while specificity was highest for younger subjects. Significant correlations were observed between atrophy ratings of hippocampus, amygdala, entorhinal cortex and parahippocampal gyrus and CAMCOG memory score and length of history. CONCLUSIONS: Temporal lobe MRI may have an important role in assisting with the clinical diagnosis of DAT, particularly its differentiation from depression and other disorders that may cause diagnostic difficulties in clinical practice.

Age Factors↗
PubMed1992

Nerve growth factor receptor-immunoreactive neurons within the developing human cortex.

A monoclonal antibody recognizing the p75 receptor for nerve growth factor (NGF) was used to assess the immunohistochemical expression of NGF receptors within the developing human neo-, limbic, and paralimbic cortices as well as the hippocampal complex. Between embryonic weeks 16 and 26, a transient population of neurons located within the upper and lower subplate zones of the neo-, limbic, and paralimbic cortices expressed the receptor for NGF. In contrast, NGF receptor-immunoreactive neurons were only observed in the upper subplate zone of the entorhinal cortex at embryonic week 40 (term), a staining pattern not observed in a 5-year-old specimen. The expression of NGF receptor-immunoreactive neurons within the upper subplate zone between embryonic weeks 16 and 40 was characterized by a dense band of immunoreactive neurons and neuropil. These neurons were bipolar with basal and apically directed neurites. NGF receptor-immunoreactive neurons were also scattered throughout the lower subplate zone and underlying white matter between embryonic weeks 19 and 26. These neurons were multipolar, with less apically directed neurites. NGF receptor-immunoreactive subplate neurons displayed a topographic distribution with the heaviest concentration found within limbic and paralimbic cortices as well as association neocortex. In contrast, light to moderate NGF receptor-immunoreactivity was seen in sensory-motor cortex. Within the hippocampal complex, only a few lightly stained NGF receptor-immunoreactive neurons were seen within the fimbria, hilar region of the dentate gyrus, and subiculum. The expression of NGF receptor-immunoreactivity increased within the subplate zone of the pre- and parasubiculum culminating in intense entorhinal cortex staining. As the entorhinal cortex merged with the developing inferior temporal association cortex, there was a marked reduction in staining intensity. In contrast to those in the subplate zone, neurons within the germinal zone and cortical plate were NGF receptor immunonegative at all times examined. The presence of NGF receptors in the subplate zone suggests that neurotrophins such as NGF play an important role in the transient viability of these neurons as well as in the guidance of cortical afferent inputs into topographically organized regions of the cerebral cortex.

Acetylcholinesterase↗
PubMed2005

Limbic system abnormalities associated with Ammon's horn sclerosis do not alter seizure outcome after amygdalohippocampectomy.

PURPOSE: To evaluate whether limbic system abnormalities associated with Ammon's horn sclerosis alter seizure outcome after selective amgydalohippocampectomy. METHODS: In 45 patients with unilateral mesial temporal lobe epilepsy, histologically proven Ammon's horn sclerosis, and uneventful postoperative course, volumes of the hippocampus, hemisphere, amygdala, entorhinal cortex, mamillary body, and fornix were measured by using a T(1)-weighted 3-D gradient-echo sequence with roughly isotropic (1.17 x 1.17 x 1-mm) voxels. In addition, signal intensity of the hippocampus and of the temporal lobe white matter was visually assessed and graded on a coronal T(2)-weighted fast-spin-echo sequence with 2-mm-thick slices. Volumetric measurements and visual analysis were compared between seizure-free and non-seizure-free patients examined 12 months after surgery. RESULTS: Hippocampal, hemispheric, entorhinal cortex, mamillary body, and fornix volumes, but not amygdalar volumes, were significantly smaller on the operated-on than on the non-operated-on side and significantly smaller in patients compared with controls. No volume differences of the hippocampus, hemisphere, amygdala, entorhinal cortex, mamillary body, and fornix existed between seizure-free (Engel class IA) and non-seizure-free patients (Engel class IB-IV). Increased temporal lobe white matter signal was observed in 15 patients but did not alter seizure outcome. CONCLUSIONS: Limbic system abnormalities are not a surrogate marker to predict postsurgical seizure outcome in patients with unilateral Ammon's horn sclerosis.

Adolescent↗
PubMed1997

Presubicular and parasubicular cortical neurons of the rat: functional separation of deep and superficial neurons in vitro.

1. The presubiculum and parasubiculum are retrohippocampal structures bordered by the subiculum and medial entorhinal cortex. Deep layer (IV-VI) neurons from this region exhibit stable synaptically triggered burst behaviour which distinguishes them from superficial layer (I-III) cells. This functional separation was examined with intracellular and field potential recordings from horizontal slices of rat brain. Neurobiotin labelling and rapid Golgi techniques were used to obtain anatomical evidence of axonal trajectories. 2. Extracellular stimulation of the subiculum, deep medial entorhinal cortex or superficial pre- or parasubiculum caused, in deep layer cells only, a short latency burst discharge which could be followed by one or more after-discharges. Bursts appeared after repetitive stimulation and were stable for the life of the slice. Each event was supported by giant excitatory postsynaptic potentials (EPSPs). Events were similar whether they were evoked in horizontal slices or slices cut perpendicular to the horizontal plane. 3. Bath application of the NMDA receptor antagonist 3-[2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP; 5 microM) elevated the threshold for evoking the giant EPSP. Higher concentrations (10-15 microM) reduced the amplitude and duration of the giant EPSP. Bath application of the AMPA receptor antagonist beta-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) eliminated the evoked EPSP. 4. In intact slices, superficial layer neurons of pre- and parasubiculum could exhibit EPSPs coincident with bursts recorded in the deep layers. However, in isolated subsections of horizontal slices or in 'vertical slices', both of which contained only pre- and/or parasubiculum, evoked or picrotoxin-induced bursts occurred only in deep layer cells. Superficial layer cells in these subsections showed no response to deep layer events. 5. Antidromic population spikes confirmed projections from superficial cell layers of pre- and parasubiculum down to their deep cell layers. Reciprocal antidromic responses were absent. 6. Axons of superficial layer stellate and pyramidal cells had horizontal collaterals and at least one ascending and one descending collateral. Branches of the descending collaterals were given off in layer V and some axons were found to reach the angular bundle. Axons of deep layer stellate and pyramidal cells also had horizontal collaterals and descending collaterals which could be traced to the angular bundle. One ascending axon collateral was found among the thirty-one deep layer cells examined morphologically. 7. We conclude that the deep layer cells of the presubiculum and parasubiculum are richly interconnected with excitatory synapses. These interconnections can generate giant excitatory synaptic potentials that support the bursting behaviour exhibited by these neurons. Any of the excitatory inputs to deep layer cells can trigger the population bursts and specific inputs from entorhinal cortex produce the after-discharges. Further, connections between superficial and deep layer cells appear to be almost exclusively in the direction of superficial to deep. The absence of significant ascending input can account for the functional separation of superficial and deep layer neurons of presubiculum and parasubiculum.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Pentylenetetrazol causes polysynaptic responses to appear in the dentate gyrus.

In a particular brain region specific changes in inhibition or excitation may be the basis of seizure initiation. Alternatively, changes in the balance of excitation and inhibition in the circuit, which may be detectable as polysynaptic responses may be more important indicators of epileptogenesis. That the appearance of polysynaptic responses precedes the initiation and, therefore, may be necessary for the onset of epileptiform activity in the hippocampal-parahippocampal circuit was tested using the chemical convulsant pentylenetetrazol. Excitation and paired-pulse inhibition were measured in CA1 and the dentate gyrus of the urethane-anaesthetized rat before and after administration of pentylenetetrazol. In addition, three polysynaptic responses were monitored. In both CA1 and the dentate gyrus, pentylenetetrazol, 100 mg/kg, caused a trend towards increased excitability and caused a relatively mild loss of inhibition. Two polysynaptic responses appeared in the dentate gyrus after the administration of pentylenetratrazol, both apparently mediated through the entorhinal cortex. A polysynaptic response of the CA1 pyramidal neurons to contralateral angular bundle stimulation was not observed. These experiments demonstrate that pentylenetetrazol will facilitate only the appearance of polysynaptic responses mediated through the entorhinal cortex. These results support the hypothesis that pentylenetetrazol has a specific action within the entorhinal cortex that may facilitate the synchronization and spread of epileptiform activity. These results are also consistent with the hypothesis that the appearance of polysynaptic responses may be necessary for the onset of epileptogenesis in the hippocampal-parahippocampal circuit.

Animals↗
PubMed2001

An improved brain slice model of nerve agent-induced seizure activity.

A brain slice model was developed to investigate the mechanisms of seizure activity induced by soman and the effectiveness of potential anticonvulsant drugs. Unlike previously reported slice studies with nerve agents, this model contains the entorhinal cortex as well as the hippocampus. This allows the study of the spread of seizure discharges within the limbic system and the development of prolonged, sustained discharges that are rarely seen in the simple hippocampal slice preparation. Soman (1 microM) induced a second population spike in the evoked field potential in the CA1 or CA3 region within 15-20 min. In almost all the slices tested, this developed into spontaneous seizure activity within 30-40 min. As well as interictal bursts, many slices also showed longer periods of high-frequency bursting analogous to ictal seizure activity that originated in the entorhinal cortex. This activity appeared similar to that induced by the muscarinic agonist pilocarpine. Both the second population spike and the spontaneous discharges could be blocked by diazepam and by AMPA/kainate antagonists, but not by the NMDA antagonists AP5 and MK-801. This study confirms that the combined hippocampal-entorhinal cortex slice preparation is a suitable model for investigating the origin and propagation of nerve-agent-induced seizures within the limbic system.

Animals↗
PubMed2000

Outgrowth-promoting molecules in the adult hippocampus after perforant path lesion.

Lesion-induced neuronal plasticity in the adult central nervous system of higher vertebrates appears to be controlled by region- and layer-specific molecules. In this study we demonstrate that membrane-bound hippocampal outgrowth-promoting molecules, as present during the development of the entorhino-hippocampal system and absent or masked in the adult hippocampus, appear 10 days after transection of the perforant pathway. We used an outgrowth preference assay to analyse the outgrowth preference of axons from postnatal entorhinal explants on alternating membrane lanes obtained from hippocampus deafferented from its entorhinal input taken 4, 10, 20, 30 and 80 days post-lesion and from adult control hippocampus. Neurites from the entorhinal cortex preferred to extend axons on hippocampal membranes disconnected from their entorhinal input for 10 days in comparison with membranes obtained from unlesioned adult animals. Membranes obtained from hippocampi disconnected from their entorhinal input for 10 days were equally as attractive for growing entorhinal cortex (EC) axons as membranes from early postnatal hippocampi. Further analysis of membrane properties in an outgrowth length assay showed that entorhinal axons extended significantly longer on stripes of lesioned hippocampal membranes in comparison with unlesioned hippocampal membranes. This effect was most prominent 10 days after lesion, a time point at which axonal sprouting and reactive synaptogenesis are at their peak. Phospholipase treatment of membranes obtained from unlesioned hippocampi of adult animals strongly promoted the outgrowth length of entorhinal axons on these membranes but did not affect their outgrowth preference for deafferented hippocampal membranes. Our results indicate that membrane-bound outgrowth-promoting molecules are reactivated in the adult hippocampus following transection of the perforant pathway, and that neonatal entorhinal axons are able to respond to these molecules. These findings support the hypothesis of a temporal accessibility of membrane-bound factors governing the layer-specific sprouting of remaining axons following perforant path lesion in vivo.

Animals↗
PubMed1997

Antidromic and orthodromic responses by subicular neurons in rat brain slices.

The subiculum forms part of the region of transition between hippocampus and entorhinal cortex and is one of the primary output structures of the hippocampal formation. Intracellular recordings from subicular bursting and non-bursting cell types and field potential recordings were taken in horizontal slices from rat brains. The inputs and outputs of the two cell types were studied for the purpose of reinforcing or refuting the dichotomy proposed on the basis of membrane properties. Some bursting cells were antidromically activated by stimuli applied to the superficial or deep layers of presubiculum, but never by stimuli applied to deep layers of medial entorhinal cortex (dMEC). Some non-bursting subicular neurons were antidromically activated by stimuli applied to dMEC, but never by stimuli applied to presubiculum. Antidromic population events in subiculum were single spikes when deep MEC was stimulated, but were bursts when presubiculum was stimulated, even in the presence of glutamate receptor antagonists. Population bursts consist of 2 or more population spikes with peak to peak intervals of approximately 5 ms. That population bursts occur in slices where excitatory transmission is blocked suggests that such population bursts reflect coincident bursts by individual neurons. Short-latency (< 5 ms) excitatory postsynaptic potentials (EPSPs) were evoked in both subicular cell types in response to single entorhinal, presubicular and CA1 stimuli. Long-latency (> 10 ms) EPSPs were seen in both cell types in response to presubicular, but not entorhinal or CA1 stimulation. Bursting cells responded to brief trains of orthodromic stimuli (2-10 pulses, 5-10 ms interstimulus interval) with a burst of action potentials even when the cell was previously depolarized out of bursting range by current injection. Non-bursting cells responded to brief trains of orthodromic stimuli with repetitive firing (< or = 1 spike/stimulus) at all holding potentials. Spike intervals could reach those seen in bursts by bursting cells. It is concluded that: (1) the distinction between bursting and non-bursting subicular neurons is a dichotomy and cells do not change their identity when activated antidromically or orthodromically; (2) the outputs of the two cell types may be different: bursting cells projected to presubiculum and non-bursting cells projected to entorhinal cortex; and (3) non-bursting cells can, when repetitively stimulated, fire repetitive spikes with interspike intervals in the range of intervals seen in bursts.

Action Potentials↗
PubMed1999

Loss of NADPH diaphorase-positive neurons in the hippocampal formation of chronic pilocarpine-epileptic rats.

Recent evidence suggests an important role for NO in cholinergic models of epilepsy. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd), a marker of NO containing neurons, was shown to intensely colocalize with GABA in double-labeling studies performed in the hippocampal formation (exception made for the pyramidal cell layer) (Valtschanoff et al., J Comp Neurol 1993:331:111-121). In this sense, it further characterizes an extremely important cell category due to the relevant involvement of inhibitory systems in the mechanisms of genesis and propagation of seizures. Here, we assessed the histochemistry for NADPHd in the hippocampal complex of chronic pilocarpine-epileptic animals. NADPHd-positive cells were lost in almost every hippocampal subfield in pilocarpine-treated rats. The central portion of the polymorphic layer of the dentate gyrus (hilus) presented one of the highest losses of NADPHd-positive cells (55-79%) in the hippocampus. A significant loss of NADPHd-positive cells was seen in strata oriens, pyramidale, and radiatum CA1, CA2, and CA3 subfields. NADPHd staining in the subicular pyramidal cell layer was not different from that observed in controls. A significant loss of NADPHd-stained cells was observed in entorhinal cortex layers II and III in the epileptic group. For entorhinal cortex layers V and VI, however, results varied from an almost complete tissue destruction to an overexpression of NADPHd-positive cells, as well as an increase in neuropil staining. In summary, loss of NADPHd staining was not uniform throughout the hippocampal formation. There has been a growing support for the notion that GABAergic neurons in the hippocampal formation are not equally sensitive to insults. Our results suggest that, as a marker for a subpopulation of GABAergic neurons, NADPHd helps in further refining the characterization of the different neuronal populations sensitive to epileptic activity.

Animals↗
PubMed2001

Tau, beta-amyloid and beta-amyloid precursor protein distribution in the entorhinal-hippocampal alvear and perforant pathways in the Alzheimer's brain.

It has been suggested that the pathological lesions of Alzheimer's disease (AD) spread along neuronal connections. This study was designed to examine this hypothesis in the alvear and perforant pathways, two well-defined neuroanatomical pathways that project from the entorhinal cortex to the hippocampus. Paraffin-sections of hippocampal-entorhinal cortex from 25 AD cases were immunolabelled for tau, beta-amyloid (Abeta) and beta-amyloid precursor protein (betaAPP). We used image-analysis to quantify immunolabelling at both ends of the alvear and perforant pathways. At the beginning and the end of the alvear pathway, area of immunolabelling in microm2 per area of field (72000 microm2) were as follows: tau 349 and 821 (P<0.01), Abeta 349 and 61 (P<0.05) and betaAPP 18 and 73 (P<0.01). Corresponding values for the perforant pathway were tau 421 and 387, Abeta 382 and 115 (P<0.05) and betaAPP 55 and 83. Tau was significantly greater at the end than at the beginning of the alvear pathway, but similar at both ends of the perforant pathway. There was significantly more Abeta at the beginning than at the end of the alvear and perforant pathway. These results at least in part reinforce previous work [19] that tau-rich areas may be neuronally connected to Abeta-rich areas.

Aged↗