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Entorhinal Cortex (entorhinal + cortex)
Kinds of Entorhinal Cortex Terms modified by Entorhinal Cortex Selected AbstractsElectrical and Chemical Long-term Depression Do Not Attenuate Low-Mg2+,induced Epileptiform Activity in the Entorhinal CortexEPILEPSIA, Issue 4 2005Jörg Solger Summary:,Purpose: Low-frequency electrical and magnetic stimulation of cortical brain regions has been shown to reduce cortical excitability and to decrease the susceptibility to seizures in humans and in vivo models of epilepsy. The induction of long-term depression (LTD) or depotentiation of a seizure-related long-term potentiation has been proposed to be part of the underlying mechanism. With the low-Mg2+ -model of epilepsy, this study investigated the effect of electrical LTD, chemical LTD, and depotentiation on the susceptibility of the entorhinal cortex to epileptiform activity. Methods: The experiments were performed on isolated entorhinal cortex slices obtained from adult Wistar rats and mice. With extracellular recording techniques, we studied whether LTD induced by (a) three episodes of low-frequency paired-pulse stimulation (3 × 900 paired pulses at 1 Hz), and by (b) bath-applied N -methyl- d -aspartate (NMDA, 20 ,M) changes time-to-onset, duration, and frequency of seizure-like events (SLEs) induced by omitting MgSO4 from the artificial cerebrospinal fluid. Next we investigated the consequences of depotentiation on SLEs themselves by applying low-frequency stimulation after onset of low-Mg2+,induced epileptiform activity. Results: LTD, induced either by low-frequency stimulation or by bath-applied NMDA, had no effect on time-to-onset, duration, and frequency of SLEs compared with unconditioned slices. Low-frequency stimulation after onset of SLEs did not suppress but induced SLEs that lasted for the time of stimulation and were associated with a simultaneous increase of the extracellular K+ concentration. Conclusions: Our study demonstrates that neither conditioning LTD nor brief low-frequency stimulation decreases the susceptibility of the entorhinal cortex to low-Mg2+,induced epileptiform activity. The present study does not support the hypothesis that low-frequency brain stimulation exerts its anticonvulsant effect via the induction of LTD or depotentiation. [source] Ibotenate Injections into the Pre- and Parasubiculum Provide Partial Protection against Kainate-Induced Epileptic Damage in Layer III of Rat Entorhinal CortexEPILEPSIA, Issue 7 2001Tore Eid Summary: ,Purpose: A loss of neurons in layer III of the entorhinal cortex (EC) is often observed in patients with temporal lobe epilepsy and in animal models of the disorder. We hypothesized that the susceptibility of layer III of the EC to prolonged seizure activity might be mediated by excitatory afferents originating in the presubiculum. Methods: Experiments were designed to ablate the presubiculum unilaterally by focal ibotenate injections and to evaluate the effect of this deafferentation on the vulnerability of EC layer III neurons to the chemoconvulsant kainate (injected systemically 5 days later). Results: After treatment with kainate, 11 of the 15 rats preinjected with ibotenate showed clear-cut, partial neuroprotection in layer III of the EC ipsilateral to the ibotenate lesion. Serial reconstruction of the ibotenate-induced primary lesion revealed that entorhinal neurons were protected only in animals that had lesions in the pre- and parasubiculum, especially in the deep layers (IV,VI). Conclusions: The deep layers of the pre- and parasubiculum appear to control the seizure-induced damage of EC layer III. This phenomenon may be of relevance for epileptogenesis and for the pathogenesis of temporal lobe epilepsy. [source] Fenfluramine Blocks Low-Mg2+ -Induced Epileptiform Activity in Rat Entorhinal CortexEPILEPSIA, Issue 8 2000K. Gentsch Summary: Purpose: The entorhinal cortex (EC) represents the main input structure to the hippocampus and seems to be critically involved in temporal lobe epilepsy. Considering that the EC receives a strong serotonergic projection from the raphe nuclei and expresses a high density of serotonin (5-HT) receptors, the effect of the 5-HT,releasing drug fenfluramine (FFA) on epileptiform activity generated in the EC was investigated in an in vitro model of epilepsy. Methods: The experiments were performed on 43 horizontal slices containing the EC, the subiculum, and the hippocampal formation obtained from 230,250 g adult Wistar rats. Using extracellular recording techniques, we investigated the effect of bath-applied FFA (200 ,mol/L to 1 mmol/L) on epileptiform activity induced by omitting MgSO4 from the artificial cerebrospinal fluid. Results: We demonstrate that FFA reversibly blocks epileptiform activity in the EC. Surprisingly, in the presence of the 5-HT uptake blocker paroxetine, the FFA-induced effect was diminished. Coapplication of the 5-HTIA receptor antagonist WAY 100635 prevented the FFA-induced anticonvulsive effect, suggesting that (a) the FFA-induced suppression of epileptiform activity is mediated by the release of 5-HT from synaptic terminals within the EC rather than by an unspecific effect of FFA and (b) released 5-HT most likely blocks the activity by activation of 5-HTIA receptors. Conclusion: FFA, which is primarily used because of its anorectic activity, might get an additional therapeutic value in the treatment of temporal lobe epilepsy with parahippocampal involvement. [source] Subfield atrophy pattern in temporal lobe epilepsy with and without mesial sclerosis detected by high-resolution MRI at 4 Tesla: Preliminary resultsEPILEPSIA, Issue 6 2009Susanne G. Mueller Summary Purpose:, High-resolution magnetic resonance imaging (MRI) at 4 Tesla depicts details of the internal structure of the hippocampus not visible at 1.5 Tesla, and so allows for in vivo parcellation of different hippocampal subfields. The aim of this study was to test if distinct subfield atrophy patterns can be detected in temporal lobe epilepsy (TLE) with mesial temporal sclerosis (TLE-MTS) and without (TLE-no) hippocampal sclerosis. Methods:, High-resolution T2 -weighted hippocampal images were acquired in 34 controls: 15 TLE-MTS and 18 TLE-no. Entorhinal cortex (ERC), subiculum (SUB), CA1, CA2, and CA3, and dentate (CA3&DG) volumes were determined using a manual parcellation scheme. Results:, TLE-MTS had significantly smaller ipsilateral CA1, CA2, CA3&DG, and total hippocampal volume than controls or TLE-no. Mean ipsilateral CA1 and CA3&DG z-scores were significantly lower than ipsilateral CA2, ERC, and SUB z-scores. There were no significant differences between the various subfield or hippocampal z-scores on either the ipsi- or the contralateral side in TLE-no. Using a z-score ,,2.0 to identify severe volume loss, the following atrophy patterns were found in TLE-MTS: CA1 atrophy, CA3&DG atrophy, CA1 and CA3&DG atrophy, and global hippocampal atrophy. Significant subfield atrophy was found in three TLE-no: contralateral SUB atrophy, bilateral CA3&DG atrophy, and ipsilateral ERC and SUB atrophy. Discussion:, Using a manual parcellation scheme on 4 Tesla high-resolution MRI, we found the characteristic ipsilateral CA1 and CA3&DG atrophy described in TLE-MTS. Seventeen percent of the TLE-no had subfield atrophy despite normal total hippocampal volume. These findings indicate that high-resolution MRI and subfield volumetry provide superior information compared to standard hippocampal volumetry. [source] Entorhinal cortex contributes to object-in-place scene memoryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2004David P. Charles Abstract Four rhesus monkeys (Macaca mulatta) were trained preoperatively in a test of object-in-place scene memory. They were presented daily with lists of unique computer-generated scenes each containing a spatial array of multiple individual objects. Within each scene, objects to be discriminated appeared in the foreground, each occupying a unique location, and monkeys were required to correctly discriminate the rewarded object to receive a food reward. Once this preoperative criterion was attained, the monkeys received bilateral entorhinal cortex ablation performed as either one or two surgical operations with a period of testing following each. Postoperatively, they were significantly impaired in learning new object-in-place scene problems. These results show that the entorhinal cortex, like anatomically related structures including the perirhinal cortex and the fornix, contributes to object-in-place scene learning. [source] Glutamine induces epileptiform discharges in superficial layers of the medial entorhinal cortex from pilocarpine-treated chronic epileptic rats in vitroEPILEPSIA, Issue 4 2009Nora Sandow Summary Purpose:, Glutamine (GLN) is a precursor for synthesis of glutamate and ,-aminobutyric acid (GABA) and has been found in the cerebrospinal fluid (CSF) at mean concentrations of 0.6 mM. Experiments on slices are usually performed in artificial CSF (aCSF) kept free of amino acids. Therefore, the role of glutamine, particularly in tissue of epileptic animals, remains elusive. Methods:, Using extracellular recordings we studied effects of GLN on field potentials and stimulus-evoked field responses in the medial entorhinal cortex (MEC) of combined entorhinal cortex hippocampal slices from pilocarpine-treated chronic epileptic rats and age-matched saline-injected control rats. Results:, In presence of GLN (0.5 and 2 mM) recurrent epileptiform discharges (REDs) were observed in slices from epileptic rats (64% and 80%, respectively), but not in slices from control rats. REDs were restricted to the superficial MEC, suppressed by the ,-Amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (30 ,M), attenuated by the inhibitor of neuronal glutamine transporters methylamino-isobutyric acid (10 mM), and apparently augmented and prolonged by the GABAA receptor antagonist bicuculline-methiodide (5 ,M). In contrast, amplitudes of stimulus evoked nonsynaptic and synaptic field responses increased in slices from control rats (+23% and +12% of the reference values) and insignificantly less or not in those of epileptic rats (+6.5% and ,0.25%, respectively). Notably, stimulus-evoked slow negative transients confined to slices of epileptic animals were reduced in amplitude (,18%). Discussion:, In combined entorhinal hippocampal slices from chronic epileptic animals, GLN induces glutamatergic REDs via neuronal uptake in superficial layers of the MEC where inhibitory function seemed to be partially preserved. [source] Propagation Dynamics of Epileptiform Activity Acutely Induced by Bicuculline in the Hippocampal,Parahippocampal Region of the Isolated Guinea Pig BrainEPILEPSIA, Issue 12 2005Laura Uva Summary:,Purpose: Aim of the study is to investigate the involvement of parahippocampal subregions in the generation and in the propagation of focal epileptiform discharges in an acute model of seizure generation in the temporal lobe induced by arterial application of bicuculline in the in vitro isolated guinea pig brain preparation. Methods: Electrophysiological recordings were simultaneously performed with single electrodes and multichannel silicon probes in the entorhinal, perirhinal, and piriform cortices and in the area CA1 of the hippocampus of the in vitro isolated guinea pig brain. Interictal and ictal epileptiform discharges restricted to the temporal region were induced by a brief (3,5 min) arterial perfusion of the GABAA receptor antagonist, bicuculline methiodide (50 ,M). Current source density analysis of laminar field profiles performed with the silicon probes was carried out at different sites to establish network interactions responsible for the generation of epileptiform potentials. Nonlinear regression analysis was conducted on extracellular recordings during ictal onset in order to quantify the degree of interaction between fast activities generated at different sites, as well as time delays. Results: Experiments were performed in 31 isolated guinea pig brains. Bicuculline-induced interictal and ictal epileptiform activities that showed variability of spatial propagation and time course in the olfactory,temporal region. The most commonly observed pattern (n = 23) was characterized by the initial appearance of interictal spikes (ISs) in the piriform cortex (PC), which propagated to the lateral entorhinal region. Independent and asynchronous preictal spikes originated in the entorhinal cortex (EC)/hippocampus and progressed into ictal fast discharges (around 25 Hz) restricted to the entorhinal/hippocampal region. The local generation of fast activity was verified and confirmed both by CSD and phase shift analysis performed on laminar profiles. Fast activity was followed by synchronous afterdischarges that propagated to the perirhinal cortex (PRC) (but not to the PC). Within 1,9 min, the ictal discharge ceased and a postictal period of depression occurred, after which periodic ISs in the PC resumed. Unlike preictal ISs, postictal ISs propagated to the PRC. Conclusions: Several studies proposed that reciprocal connections between the entorhinal and the PRC are under a very efficient inhibitory control (1). We report that ISs determined by acute bicuculline treatment in the isolated guinea pig brain progress from the PC to the hippocampus/EC just before ictal onset. Ictal discharges are characterized by a peculiar pattern of fast activity that originates from the entorhinal/hippocampal region and only secondarily propagates to the PRC. Postictal propagation of ISs to the PRC occured exclusively when an ictal discharge was generated in the hippocampal/entorhinal region. The results suggest that reiteration of ictal events may promote changes in propagation pattern of epileptiform discharges that could act as trigger elements in the development of temporal lobe epilepsy. [source] Electrical and Chemical Long-term Depression Do Not Attenuate Low-Mg2+,induced Epileptiform Activity in the Entorhinal CortexEPILEPSIA, Issue 4 2005Jörg Solger Summary:,Purpose: Low-frequency electrical and magnetic stimulation of cortical brain regions has been shown to reduce cortical excitability and to decrease the susceptibility to seizures in humans and in vivo models of epilepsy. The induction of long-term depression (LTD) or depotentiation of a seizure-related long-term potentiation has been proposed to be part of the underlying mechanism. With the low-Mg2+ -model of epilepsy, this study investigated the effect of electrical LTD, chemical LTD, and depotentiation on the susceptibility of the entorhinal cortex to epileptiform activity. Methods: The experiments were performed on isolated entorhinal cortex slices obtained from adult Wistar rats and mice. With extracellular recording techniques, we studied whether LTD induced by (a) three episodes of low-frequency paired-pulse stimulation (3 × 900 paired pulses at 1 Hz), and by (b) bath-applied N -methyl- d -aspartate (NMDA, 20 ,M) changes time-to-onset, duration, and frequency of seizure-like events (SLEs) induced by omitting MgSO4 from the artificial cerebrospinal fluid. Next we investigated the consequences of depotentiation on SLEs themselves by applying low-frequency stimulation after onset of low-Mg2+,induced epileptiform activity. Results: LTD, induced either by low-frequency stimulation or by bath-applied NMDA, had no effect on time-to-onset, duration, and frequency of SLEs compared with unconditioned slices. Low-frequency stimulation after onset of SLEs did not suppress but induced SLEs that lasted for the time of stimulation and were associated with a simultaneous increase of the extracellular K+ concentration. Conclusions: Our study demonstrates that neither conditioning LTD nor brief low-frequency stimulation decreases the susceptibility of the entorhinal cortex to low-Mg2+,induced epileptiform activity. The present study does not support the hypothesis that low-frequency brain stimulation exerts its anticonvulsant effect via the induction of LTD or depotentiation. [source] High-frequency Oscillations after Status Epilepticus: Epileptogenesis and Seizure GenesisEPILEPSIA, Issue 9 2004Anatol Bragin Summary:,Purpose: To investigate the temporal relation between high-frequency oscillations (HFOs) in the dentate gyrus and recurrent spontaneous seizures after intrahippocampal kainite-induced status epilepticus. Methods: Recording microelectrodes were implanted bilaterally in different regions of hippocampus and entorhinal cortex. A guide cannula for microinjection of kainic acid (KA) was implanted above the right posterior CA3 area of hippocampus. After recording baseline electrical activity, KA (0.4 ,g/0.2 ,l) was injected. Beginning on the next day, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for ,30 days. Results: Of the 26 rats studied, 19 revealed the appearance of sharp-wave activity and HFOs in the frequency range of 80 to 500 Hz in the dentate gyrus ipsilateral to the KA injection. In the remaining seven rats, no appreciable activity was noted in this frequency range. In some rats with recurrent seizures, HFOs were in the ripple frequency range (100,200 Hz); in others, HFOs were in the fast ripple frequency range (200,500 Hz), or a mixture of both oscillation frequencies was found. The time of detection of the first HFOs after status epilepticus varied between 1 and 30 days, with a mean of 6.3 ± 2.0 (SEM). Of the 19 rats in which HFO activity appeared, all later developed recurrent spontaneous seizures, whereas none of the rats without HFOs developed seizures. The sooner HFO activity was detected after status epilepticus, the sooner the first spontaneous seizure occurred. A significant inverse relation was found between the time to the first HFO detection and the subsequent rate of spontaneous seizures. Conclusions: A strong correlation was found between a decreased time to detection of HFOs and an increased rate of spontaneous seizures, as well as with a decrease in the duration of the latent period between KA injection and the detection of spontaneous seizures. Two types of HFOs were found after KA injection, one in the frequency range of 100 to 200 Hz, and the other, in the frequency range of 200 to 500 Hz, and both should be considered pathological, suggesting that both are epileptogenic. [source] Ibotenate Injections into the Pre- and Parasubiculum Provide Partial Protection against Kainate-Induced Epileptic Damage in Layer III of Rat Entorhinal CortexEPILEPSIA, Issue 7 2001Tore Eid Summary: ,Purpose: A loss of neurons in layer III of the entorhinal cortex (EC) is often observed in patients with temporal lobe epilepsy and in animal models of the disorder. We hypothesized that the susceptibility of layer III of the EC to prolonged seizure activity might be mediated by excitatory afferents originating in the presubiculum. Methods: Experiments were designed to ablate the presubiculum unilaterally by focal ibotenate injections and to evaluate the effect of this deafferentation on the vulnerability of EC layer III neurons to the chemoconvulsant kainate (injected systemically 5 days later). Results: After treatment with kainate, 11 of the 15 rats preinjected with ibotenate showed clear-cut, partial neuroprotection in layer III of the EC ipsilateral to the ibotenate lesion. Serial reconstruction of the ibotenate-induced primary lesion revealed that entorhinal neurons were protected only in animals that had lesions in the pre- and parasubiculum, especially in the deep layers (IV,VI). Conclusions: The deep layers of the pre- and parasubiculum appear to control the seizure-induced damage of EC layer III. This phenomenon may be of relevance for epileptogenesis and for the pathogenesis of temporal lobe epilepsy. [source] Comparison of Intrinsic Optical Signals Associated with Low Mg2+, and 4-Aminopyridine,Induced Seizure-Like Events Reveals Characteristic Features in Adult Rat Limbic SystemEPILEPSIA, Issue 6 2000Katharina Buchheim Summary: Purpose: To analyze the intrinsic optical signal change associated with seizure-like events in two frequently used in vitro models,the low-Mg2+ and the 4-aminopyridine (4-AP) models,and to monitor regions of onset and spread patterns of these discharges by using imaging of intrinsic optical signals (IOS). Methods: Combined hippocampal,entorhinal,cortex slices of adult rats were exposed to two different treatments: lowering extracellular Mg2+ concentrations or application of 100 ,M 4-AP. The electrographic features of the discharges were monitored using extracellular microelectrodes. Optical imaging was achieved by infrared transillumination of the slice and analysis of changes in light transmission using a subtraction approach. The electrographic features were compared with the optical changes. Regions of onset and spread patterns were analyzed in relevant anatomic regions of the slice. Results: Both lowering extracellular Mg2+ concentrations and application of 4-AP induced seizure-like events. The relative duration of the intrinsic optical signal change associated with seizure-like events in the low-Mg2+ model was significantly longer compared with that seen with those occurring in the 4-AP model, although duration of field potentials did not differ significantly in the two models. Seizure-like events of the low-Mg2+ model originated predominantly in the entorhinal cortex, with subsequent propagation toward the subiculum and neocortical structures. In contrast, no consistent region of onset or spread patterns were seen in the 4-AP model, indicating that the seizure initiation is not confined to a particular region in this model. Conclusions: We conclude that different forms of spontaneous epileptiform activity are associated with characteristic optical signal changes and that optical imaging represents an excellent method to assess regions of seizure onset and spread patterns. [source] Muscarinic control of graded persistent activity in lateral amygdala neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006Alexei V. Egorov Abstract The cholinergic system is crucially involved in several cognitive processes including attention, learning and memory. Muscarinic actions have profound effects on the intrinsic firing pattern of neurons. In principal neurons of the entorhinal cortex (EC), muscarinic receptors activate an intrinsic cation current that causes multiple self-sustained spiking activity, which represents a potential mechanism for transiently sustaining information about novel items. The amygdala appears to be important for experience-dependent learning by emotional arousal, and cholinergic muscarinic influences are essential for the amygdala-mediated modulation of memory. Here we show that principal neurons from the lateral nucleus of the amygdala (LA) can generate intrinsic graded persistent activity that is similar to EC layer V cells. This firing behavior is linked to muscarinic activation of a calcium-sensitive non-specific cation current and can be mimicked by stimulation of cholinergic afferents that originate from the nucleus basalis of Meynert (n. M). Moreover, we demonstrate that the projections from the n. M. are essential and sufficient for the control and modulation of graded firing activity in LA neurons. We found that activation of these cholinergic afferents (i) is required to maintain and to increase firing rates in a graded manner, and (ii) is sufficient for the graded increases of stable discharge rates even without an associated up-regulation of Ca2+. The induction of persistent activity was blocked by flufenamic acid or 2-APB and remained intact after Ca2+ -store depletion with thapsigargin. The internal ability of LA neurons to generate graded persistent activity could be essential for amygdala-mediated memory operations. [source] Differential effects of low glucose concentrations on seizures and epileptiform activity in vivo and in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2006Anne Kirchner Abstract In vivo, severe hypoglycemia is frequently associated with seizures. The hippocampus is a structure prone to develop seizures and seizure-induced damage. Patients with repeated hypoglycemic episodes have frequent memory problems, suggesting impaired hippocampal function. Here we studied the effects of moderate hypoglycemia on primarily generalized flurothyl-induced seizures in vivo and, using EEG recordings, we determined involvement of the hippocampus in hypoglycemic seizures. Moderate systemic hypoglycemia had proconvulsant effects on flurothyl-induced clonic (forebrain) seizures. During hypoglycemic seizures, seizure discharges were recorded in the hippocampus. Thus, we continued the studies in combined entorhinal cortex,hippocampus slices in vitro. However, in vitro, decreases in extracellular glucose from baseline 10 mm to 2 or 1 mm did not induce any epileptiform discharges. In fact, low glucose (2 and 1 mm) attenuated preexisting low-Mg2+ -induced epileptiform activity in the entorhinal cortex and hippocampal CA1 region. Osmolarity compensation in low-glucose solution using mannitol impaired slice recovery. Additionally, using paired-pulse stimuli we determined that there was no impairment of GABAA inhibition in the dentate gyrus during glucopenia. The data strongly indicate that, although forebrain susceptibility to seizures is increased during moderate in vivo hypoglycemia and the hippocampus is involved during hypoglycemic seizures, glucose depletion in vitro contributes to an arrest of epileptiform activity in the system of the entorhinal cortex,hippocampus network and there is no impairment of net GABAA inhibition during glucopenia. [source] The role of the medial temporal lobe in autistic spectrum disordersEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2005C. H. Salmond Abstract The neural basis of autistic spectrum disorders (ASDs) is poorly understood. Studies of mnemonic function in ASD suggest a profile of impaired episodic memory with relative preservation of semantic memory (at least in high-functioning individuals). Such a pattern is consistent with developmental hippocampal abnormality. However, imaging evidence for abnormality of the hippocampal formation in ASD is inconsistent. These inconsistencies led us to examine the memory profile of children with ASD and the relationship to structural abnormalities. A cohort of high-functioning individuals with ASD and matched controls completed a comprehensive neuropsychological memory battery and underwent magnetic resonance imaging for the purpose of voxel-based morphometric analyses. Correlations between cognitive/behavioural test scores and quantified results of brain scans were also carried out to further examine the role of the medial temporal lobe in ASD. A selective deficit in episodic memory with relative preservation of semantic memory was found. Voxel-based morphometry revealed bilateral abnormalities in several areas implicated in ASD including the hippocampal formation. A significant correlation was found between parental ratings reflecting autistic symptomatology and the measure of grey matter density in the junction area involving the amygdala, hippocampus and entorhinal cortex. The data reveal a pattern of impaired and relatively preserved mnemonic function that is consistent with a hippocampal abnormality of developmental origin. The structural imaging data highlight abnormalities in several brain regions previously implicated in ASD, including the medial temporal lobes. [source] Entorhinal cortex contributes to object-in-place scene memoryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2004David P. Charles Abstract Four rhesus monkeys (Macaca mulatta) were trained preoperatively in a test of object-in-place scene memory. They were presented daily with lists of unique computer-generated scenes each containing a spatial array of multiple individual objects. Within each scene, objects to be discriminated appeared in the foreground, each occupying a unique location, and monkeys were required to correctly discriminate the rewarded object to receive a food reward. Once this preoperative criterion was attained, the monkeys received bilateral entorhinal cortex ablation performed as either one or two surgical operations with a period of testing following each. Postoperatively, they were significantly impaired in learning new object-in-place scene problems. These results show that the entorhinal cortex, like anatomically related structures including the perirhinal cortex and the fornix, contributes to object-in-place scene learning. [source] Topographic distribution of direct and hippocampus- mediated entorhinal cortex activity evoked by olfactory tract stimulationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2004Vadym Gnatkovsky Abstract Olfactory information is central for memory-related functions, such as recognition and spatial orientation. To understand the role of olfaction in learning and memory, the distribution and propagation of olfactory tract-driven activity in the parahippocampal region needs to be characterized. We recently demonstrated that repetitive stimulation of the olfactory tract in the isolated guinea pig brain preparation induces an early direct activation of the rostrolateral entorhinal region followed by a delayed response in the medial entorhinal cortex (EC), preceded by the interposed activation of the hippocampus. In the present study we performed a detailed topographic analysis of both the early and the delayed entorhinal responses induced by patterned stimulation of the lateral olfactory tract in the isolated guinea pig brain. Bi-dimensional maps of EC activity recorded at 128 recording sites with 4 × 4 matrix electrodes (410 µm interlead separation) sequentially placed in eight different positions, showed (i) an early (onset at 16.09 ± 1.2 ms) low amplitude potential mediated by the monosynaptic LOT input, followed by (ii) an associative potential in the rostral EC which originates from the piriform cortex (onset at 33.2 ± 2.3 ms), and (iii) a delayed potential dependent on the previous activation of the hippocampus. The sharp component of the delayed response had an onset latency between 52 and 63 ms and was followed by a slow wave. Laminar profile analysis demonstrated that in the caudomedial EC the delayed response was associated with two distinct current sinks located in deep and in superficial layers, whereas in the rostrolateral EC a small-amplitude sink could be detected in the superficial layers exclusively. The present report demonstrates that the output generated by the hippocampal activation is unevenly distributed across different EC subregions and indicates that exclusively the medial and caudal divisions receive a deep-layer input from the hippocampus. In the rostrolateral EC, specific network interactions may be generated by the convergence of the direct olfactory input and the olfaction-driven hippocampal output. [source] Electrophysiological characterization of interlaminar entorhinal connections: an essential link for re-entrance in the hippocampal,entorhinal systemEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003Fabian Kloosterman Abstract 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. [source] Disabled-1 mRNA and protein expression in developing human cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Gundela Meyer Abstract Disabled-1 (Dab1) forms part of the Reelin,Dab1 signalling pathway that controls neuronal positioning during brain development; Dab1 deficiency gives rise to a reeler-like inversion of cortical layers. To establish a timetable of Dab1 expression in developing human brain, Dab1 mRNA and protein expression were studied in prenatal human cortex. The earliest Dab1 signal was detected at 7 gestational weeks (GW), the stage of transition from preplate to cortical plate, suggesting a role of the Reelin,Dab1 signalling pathway in preplate partition. From 12 to 20 GW, the period of maximum cortical migration, Dab1 expression was prominent in the upper tiers of the cortical plate, to decline after midgestation. Radially orientated apical dendrites of Dab1-expressing neurons indicated a predominant pyramidal phenotype. Pyramidal cells in hippocampus and entorhinal cortex displayed a more protracted time of Dab1 expression compared to neocortex. In addition, at later stages (18,25 GW), Dab1 was also expressed in large neurons scattered throughout intermediate zone and subplate. From 14 to 22 GW, particularly high levels of Dab1 mRNA and protein were observed in cells of the ventricular/subventricular zone displaying the morphology of radial glia. The partial colocalization of vimentin and Dab1 in cells of the ventricular zone supported a radial glia phenotype. The concentration of Dab1 protein in ventricular endfeet and initial portions of radial processes of ventricular-zone cells points to a possible involvement of Dab1 in neurogenesis. Furthermore, a subset of Cajal,Retzius cells in the marginal zone colocalized Dab1 and Reelin, and may thus represent a novel target of the Reelin,Dab1 signalling pathway. [source] Glutamate transporter expression in astrocytes of the rat dentate gyrus following lesion of the entorhinal cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2001C. Hein Abstract The glutamate transporters GLT-1 and GLAST localized in astrocytes are essential in limiting transmitter signalling and restricting harmful receptor overstimulation. To show changes in the expression of both transporters following lesion of the entorhinal cortex (and degeneration of the glutamatergic tractus perforans), quantitative microscopic in situ hybridization (ISH) using alkaline-phosphatase-labelled oligonucleotide probes was applied to the outer molecular layer of the hippocampal dentate gyrus of rats (termination field of the tractus perforans). Four groups of rats were studied: sham-operated controls, and animals 3, 14 and 60 days following unilateral electrolytic lesion of the entorhinal cortex. The postlesional shrinkage of the terminal field of the perforant path, ipsilateral to the lesion side, was determined and considered in the evaluation of quantitative ISH data. Statistical analysis revealed that ipsilateral to the lesion side there was a significant decrease of the GLT-1 mRNA at every postlesional time-point and of the GLAST mRNA at 14 and 60 days postlesion. The maximal decrease was ,,45% for GLT-1 and ,,35% for GLAST. In the terminal field of the perforant path contralateral to the lesion side, no significant changes of ISH labelling were measured. The results were complemented by immunocytochemical data achieved using antibodies against synthetic GLT-1 and GLAST peptides. In accordance with ISH results, there was an obvious decrease of GLT-1 and GLAST immunostaining in the terminal field of the perforant path ipsilateral to the lesion side. From these data we conclude that, following a lesioning of the entorhinal cortex, the loss of glutamatergic synapses in the terminal field of the perforant path resulted in a strong downregulation of glutamate transporters in astrocytes. The decrease of synaptically released glutamate or of other neuronal factors could be involved in this downregulation. [source] Functional connections and epileptic spread between hippocampus, entorhinal cortex and amygdala in a modified horizontal slice preparation of the rat brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2000Ron Stoop Abstract The hippocampus, the entorhinal cortex and the amygdala are interconnected structures of the limbic system that are implicated in memory and emotional behaviour. They demonstrate synaptic plasticity and are susceptible to development of temporal lobe epilepsy, which may lead to emotional and psychological disturbances. Their relative anatomical disposition has limited the study of neurotransmission and epileptic spread between these three regions in previous in vitro preparations. Here we describe a novel, modified-horizontal slice preparation that includes in the same plane the hippocampus, entorhinal cortex and amygdala. We found that, following application of bicuculline, each region in our preparation could generate spontaneous bursts that resembled epileptic interictal spikes. This spontaneous activity initiated in the hippocampal CA3/2 region, from where it propagated and controlled the activity in the entorhinal cortex and the amygdala. We found that this spontaneous bursting activity could spread via two different pathways. The first pathway comprises the well-known subiculum,entorhinal cortex,perirhinal cortex,amygdala route. The second pathway consists of a direct connection between the CA1 region and perirhinal cortex, through which the hippocampal bursting activity can spread to the amygdala while bypassing the entorhinal cortex. Thus, our experiments provide a new in vitro model of initiation and spread of epileptic-like activity in the ventral part of the limbic system, which includes a novel, fast and functional connection between the CA1 region and perirhinal cortex. [source] KCa2 channels transiently downregulated during spatial learning and memory in ratsHIPPOCAMPUS, Issue 3 2010Bedel Mpari Abstract Small-conductance calcium-activated potassium channels (KCa2) are essential components involved in the modulation of neuronal excitability, underlying learning and memory. Recent evidence suggests that KCa2 channel activity reduces synaptic transmission in a postsynaptic NMDA receptor-dependent manner and is modulated by long-term potentiation. We used radioactive in situ hybridization and apamin binding to investigate the amount of KCa2 subunit mRNA and KCa2 proteins in brain structures involved in learning and memory at different stages of a radial-arm maze task in naive, pseudoconditioned, and conditioned rats. We observed significant differences in KCa2.2 and KCa2.3, but not KCa2.1 mRNA levels, between conditioned and pseudoconditioned rats. KCa2.2 levels were transiently reduced in the dorsal CA fields of the hippocampus, whereas KCa2.3 mRNA levels were reduced in the dorsal and ventral CA fields of the hippocampus, entorhinal cortex, and basolateral amygdaloid nucleus in conditioned rats, during early stages of learning. Levels of apamin-binding sites displayed a similar pattern to KCa2 mRNA levels during learning. Spatial learning performance was positively correlated with levels of apamin-binding sites and KCa2.3 mRNA in the dorsal CA1 field and negatively correlated in the dorsal CA3 field. These findings suggest that KCa2 channels are transiently downregulated in the early stages of learning and that regulation of KCa2 channel levels is involved in the modification of neuronal substrates underlying new information acquisition. © 2009 Wiley-Liss, Inc. [source] Spatial learning results in elevated agmatine levels in the rat brainHIPPOCAMPUS, Issue 11 2008Ping Liu Abstract Accumulating evidence suggests that agmatine, a metabolite of L -arginine by arginine decarboxylase, is a novel neurotransmitter, and exogenous agmatine can modulate behavior functions including learning and memory. However, direct evidence of its involvement in learning and memory processes is currently lacking. This study measured agmatine levels in the hippocampus, parahippocampal region, cerebellum, and vestibular nucleus in rats that were trained to find a hidden escape platform in the water-maze task, or forced to swim in the pool with no platform presented, or kept in the holding-box, using liquid chromatography/mass spectrometry. Compared with the swimming only group and holding-box group, agmatine levels were significantly increased in the CA1 and dentate gyrus subregions of the hippocampus, the entorhinal cortex and the vestibular nucleus in the water-maze training group. These results, for the first time, demonstrate spatial learning-induced region-specific elevation in agmatine, and raise a novel issue of the involvement of agmatine in the processes of learning and memory. © 2008 Wiley-Liss, Inc. [source] Running induces widespread structural alterations in the hippocampus and entorhinal cortexHIPPOCAMPUS, Issue 11 2007Alexis M. Stranahan Abstract Physical activity enhances hippocampal function but its effects on neuronal structure remain relatively unexplored outside of the dentate gyrus. Using Golgi impregnation and the lipophilic tracer DiI, we show that long-term voluntary running increases the density of dendritic spines in the entorhinal cortex and hippocampus of adult rats. Exercise was associated with increased dendritic spine density not only in granule neurons of the dentate gyrus, but also in CA1 pyramidal neurons, and in layer III pyramidal neurons of the entorhinal cortex. In the CA1 region, changes in dendritic spine density are accompanied by changes in dendritic arborization and alterations in the morphology of individual spines. These findings suggest that physical activity exerts pervasive effects on neuronal morphology in the hippocampus and one of its afferent populations. These structural changes may contribute to running-induced changes in cognitive function. © 2007 Wiley-Liss, Inc. [source] Memory in the aging brain: Doubly dissociating the contribution of the hippocampus and entorhinal cortexHIPPOCAMPUS, Issue 11 2007Andrew P. Yonelinas Abstract Since the time of Aristotle it has been thought that memories can be divided into two basic types; conscious recollections and familiarity-based judgments. Neuropsychological studies have provided indirect support for this distinction by suggesting that different regions within the human medial temporal lobe (MTL) are involved in these two forms of memory, but none of these studies have demonstrated that these brain regions can be fully dissociated. In a group of nondemented elderly subjects, we found that performance on recall and recognition tests was predicted preferentially by hippocampal and entorhinal volumes, respectively. Structural equation modeling revealed a double dissociation, whereby age-related reductions in hippocampal volume resulted in decreases in recollection, but not familiarity, whereas entorhinal volume was preferentially related to familiarity. The results demonstrate that the forms of episodic memory supported by the human hippocampus and entorhinal cortex can be fully dissociated, and indicate that recollection and familiarity reflect neuroanatomically distinct memory processes. © 2007 Wiley-Liss, Inc. [source] Contrasting roles of neural firing rate and local field potentials in human memoryHIPPOCAMPUS, Issue 8 2007Arne Ekstrom Abstract Recording the activity of neurons is a mainstay of animal memory research, while human recordings are generally limited to the activity of large ensembles of cells. The relationship between ensemble activity and neural firing rate during declarative memory processes, however, remains unclear. We recorded neurons and local field potentials (LFPs) simultaneously from the same sites in the human hippocampus and entorhinal cortex (ERC) in patients with implanted intracranial electrodes during a virtual taxi-driver task that also included a memory retrieval component. Neurons increased their firing rate in response to specific passengers or landmarks both during navigation and retrieval. Although we did not find item specificity in the broadband LFP, both ,- and ,-band LFPs increased power to specific items on a small but significant percent of channels. These responses, however, did not correlate with item-specific neural responses. To contrast item-specific responses with process-specific responses during memory, we compared neural and LFP responses during encoding (navigation) and retrieval (associative and item-specific recognition). A subset of neurons also altered firing rates nonspecifically while subjects viewed items during encoding. Interestingly, LFPs in the hippocampus and ERC increased in power nonspecifically while subjects viewed items during retrieval, more often during associative than item-recognition. Furthermore, we found no correlation between neural firing rate and broadband, ,-band, and ,-band LFPs during process-specific responses. Our findings suggest that neuronal firing and ensemble activity can be dissociated during encoding, item-maintenance, and retrieval in the human hippocampal area, likely relating to functional properties unique to this region. © 2007 Wiley-Liss, Inc. [source] Switching between "On" and "Off" states of persistent activity in lateral entorhinal layer III neurons,HIPPOCAMPUS, Issue 4 2007Babak Tahvildari Abstract Persistent neural spiking maintains information during a working memory task when a stimulus is no longer present. During retention, this activity needs to be stable to distractors. More importantly, when retention is no longer relevant, cessation of the activity is necessary to enable processing and retention of subsequent information. Here, by means of intracellular recording with sharp microelectrode in in vitro rat brain slices, we demonstrate that single principal layer III neurons of the lateral entorhinal cortex (EC) generate persistent spiking activity with a novel ability to reliably toggle between spiking activity and a silent state. Our data indicates that in the presence of muscarinic receptor activation, persistent activity following an excitatory input may be induced and that a subsequent excitatory input can terminate this activity and cause the neuron to return to a silent state. Moreover, application of inhibitory hyperpolarizing stimuli is neither able to decrease the frequency of the persistent activity nor terminate it. The persistent activity can also be initiated and terminated by synchronized synaptic stimuli of layer II/III of the perirhinal cortex. The neuronal ability to switch "On" and "Off" persistent activity may facilitate the concurrent representation of temporally segregated information arriving in the EC and being directed toward the hippocampus. © 2007 Wiley-Liss, Inc. [source] Cholinergic suppression of excitatory synaptic responses in layer II of the medial entorhinal cortexHIPPOCAMPUS, Issue 2 2007Bassam N. Hamam Abstract Theta-frequency (4,12 Hz) electroencephalographic activity is thought to play a role in mechanisms mediating sensory and mnemonic processing in the entorhinal cortex and hippocampus, but the effects of acetylcholine on excitatory synaptic inputs to the entorhinal cortex are not well understood. Field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of the piriform (olfactory) cortex were recorded in the medial entorhinal cortex during behaviors associated with theta activity (active mobility) and were compared with those recorded during nontheta behaviors (awake immobility and slow wave sleep). Synaptic responses were smaller during behavioral activity than during awake immobility and sleep, and responses recorded during movement were largest during the negative phase of the theta rhythm. Systemic administration of cholinergic agonists reduced the amplitude of fEPSPs, and the muscarinic receptor blocker scopolamine strongly enhanced fEPSPs, suggesting that the theta-related suppression of fEPSPs is mediated in part by cholinergic inputs. The reduction in fEPSPs was investigated using in vitro intracellular recordings of EPSPs in Layer II neurons evoked by stimulation of Layer I afferents. Constant bath application of the muscarinic agonist carbachol depolarized membrane potential and suppressed EPSP amplitude in Layer II neurons. The suppression of EPSPs was not associated with a substantial change in input resistance, and could not be accounted for by a depolarization-induced reduction in driving force on the EPSP. The GABAA receptor-blocker bicuculline (50 ,M) did not prevent the cholinergic suppression of EPSPs, suggesting that the suppression is not dependent on inhibitory mechanisms. Paired-pulse facilitation of field and intracellular EPSPs were enhanced by carbachol, indicating that the suppression is likely due to inhibition of presynaptic glutamate release. These results indicate that, in addition to well known effects on postsynaptic conductances that increase cellular excitability, cholinergic activation in the entorhinal cortex results in a strong reduction in strength of excitatory synaptic inputs from the piriform cortex. © 2006 Wiley-Liss, Inc. [source] From grid cells to place cells: A mathematical modelHIPPOCAMPUS, Issue 12 2006Trygve Solstad Abstract Anatomical connectivity and recent neurophysiological results imply that grid cells in the medial entorhinal cortex are the principal cortical inputs to place cells in the hippocampus. The authors propose a model in which place fields of hippocampal pyramidal cells are formed by linear summation of appropriately weighted inputs from entorhinal grid cells. Single confined place fields could be formed by summing input from a modest number (10,50) of grid cells with relatively similar grid phases, diverse grid orientations, and a biologically plausible range of grid spacings. When the spatial phase variation in the grid-cell input was higher, multiple, and irregularly spaced firing fields were formed. These observations point to a number of possible constraints in the organization of functional connections between grid cells and place cells. © 2006 Wiley-Liss, Inc. [source] The immunosuppressant mycophenolate mofetil improves preservation of the perforant path in organotypic hippocampal slice cultures: A retrograde tracing studyHIPPOCAMPUS, Issue 5 2006Tilman M. Oest Abstract Previous studies with excitotoxically lesioned organotypic hippocampal slice cultures (OHSC) have revealed that the immunosuppressant mycophenolate mofetil (MMF) inhibits microglial activation and suppresses neuronal injury in the dentate gyrus. We here investigate whether MMF also has beneficial effects on axon survival in a long-range projection, the perforant path. Complex OHSC including the entorhinal cortex were obtained from Wistar rats (p8); the plane of section ensuring that perforant path integrity was preserved. These preparations were cultured for 9 days in vitro with or without MMF (100 ,g/ml). After fixation, the perforant path was retrogradely labeled by application of the fluorescent dye DiI (1,1,-dioctadecyl-3,3,3,,3,-tetramethylindo-carbocyanine) in the hilus of the dentate gyrus, and neuronal perikarya were immunohistochemically stained by the neuron-specific marker NeuN. Analysis of DiI-labeled and NeuN-stained OHSC by confocal laser scanning microscopy revealed double-labeled neurons in the entorhinal cortex, which projected to the dentate gyrus via the perforant path. Quantitative analysis showed that the number of these double-labeled neurons was 19-fold higher in OHSC treated with MMF than in control cultures (P < 0.05). Our findings indicate that MMF treatment improves preservation of the perforant path and encourage further studies on development and regeneration of long-range projections under the influence of immunosuppressants. © 2006 Wiley-Liss, Inc. [source] Entorhinal cortex lesions disrupt fear conditioning to background context but spare fear conditioning to a tone in the ratHIPPOCAMPUS, Issue 2 2006M. Majchrzak Abstract Recent studies have shown that the integrity of the entorhinal cortex (EC) is not required for simple contextual conditioning. In background contextual conditioning, i.e., when a phasic cue is present during training, the involvement of the EC is still a matter of debate. Therefore, the present work further examines whether the EC is required for background contextual conditioning using a tone as the phasic cue. Rats sustaining either excitotoxic lesions of the EC or sham-lesions were trained with one of two procedures differing with respect to the predictive value of the tone: a paired procedure in which the tone perfectly predicts shock occurrence and overshadows context, and an unpaired procedure in which the predictive value of the tone is reduced. Conditioned fear was assessed by freezing responses during conditioning, reexposure to the training context, and reexposure to the tone in a new context. Postshock freezing was reduced in rats with entorhinal lesions. In all rats trained with the paired procedure, freezing to the context was low and freezing to the tone was high, suggesting that the tone has overshadowed the context during the conditioning session. The reverse pattern was observed with the unpaired procedure in sham-operated rats. In rats with entorhinal lesions trained with the unpaired procedure, freezing responses to the context was markedly reduced. In a new context, however, entorhinal-lesioned rats showed higher freezing scores than those of sham-lesioned rats. Freezing to the tone was unaffected by the lesion irrespective of the tone's predictive value. As a whole, these results support the notion that the EC is required for normal background contextual freezing. © 2005 Wiley-Liss, Inc. [source] | |||||||||||||