Lateral entorhinal cortex lesions rearrange afferents, glutamate receptors, increase seizure latency and suppress seizure‐induced c‐<i>fos</i>expression in the hippocampus of adult rat

Kopniczky, Zsolt; Dobó, Endre; Borbély, Sándor; Világi, Ildikó; Détári, László; Krisztin-Péva, Beáta; Bagosi, Andrea; Molnár, Elek; Mihály, András

doi:10.1111/j.1471-4159.2005.03347.x

Cited by 27 publications

(46 citation statements)

References 67 publications

(189 reference statements)

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“…The same study also found that reactive astrocytes maintained the domain organization after deafferentation of the dentate gyrus (Wilhelmsson et al, 2006). This injury model is only inconsistently associated with seizure pathology (Kopniczky et al, 2005), thus indirectly supporting the conclusion that loss of astrocytic domain organization is restricted to pathologies associated with EEG abnormalities.…”

Section: Discussionsupporting

confidence: 62%

Loss of Astrocytic Domain Organization in the Epileptic Brain

et al. 2008

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Gliosis is a pathological hallmark of posttraumatic epileptic foci, but little is known about these reactive astrocytes beyond their high glial fibrillary acidic protein (GFAP) expression. Using diolistic labeling, we show that cortical astrocytes lost their nonoverlapping domain organization in three mouse models of epilepsy: posttraumatic injury, genetic susceptibility, and systemic kainate exposure. Neighboring astrocytes in epileptic mice showed a 10-fold increase in overlap of processes. Concurrently, spine density was increased on dendrites of excitatory neurons. Suppression of seizures by the common antiepileptic, valproate, reduced the overlap of astrocytic processes. Astrocytic domain organization was also preserved in APP transgenic mice expressing a mutant variant of human amyloid precursor protein despite a marked upregulation of GFAP. Our data suggest that loss of astrocytic domains was not universally associated with gliosis, but restricted to seizure pathologies. Reorganization of astrocytes may, in concert with dendritic sprouting and new synapse formation, form the structural basis for recurrent excitation in the epileptic brain.

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Section: Discussionsupporting

confidence: 62%

Loss of Astrocytic Domain Organization in the Epileptic Brain

et al. 2008

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“…When processing the images, each was treated identically to allow comparison of pixel densities in different hippocampal and cortical regions. The pixel density of immunoreactivity was measured by an experimenter blind to the experimental conditions using a previously established quantification strategy (Kopniczky et al, 2005). Briefly, open circular cursors with a diameter of 0.30 mm were placed on the striatum (eight circles) and perirhinal cortex (four circles; as illustrated in Fig.…”

Section: Histoblot Analysis Of Ampa and Nmda Receptor Protein Expressionmentioning

confidence: 99%

“…Brains from three wild-type (mGluR7 ϩ/ϩ ) and three mGluR7-deficient transgenic (mGluR7 Ϫ/Ϫ ) adult mice were used to determine changes in the distribution of AMPA-and NMDA-type ionotropic glutamate receptor (iGluR) subunit proteins, using an in situ blotting technique (histoblot) (Kopniczky et al, 2005). In brief, animals were deeply anesthetized and decapitated, and the brains were quickly frozen in isopentane and stored at Ϫ80°C until sectioning.…”

Section: Histoblot Analysis Of Ampa and Nmda Receptor Protein Expressionmentioning

confidence: 99%

“…This histoblot method is a reliable and convenient way to compare the regional distribution and expression pattern of different receptor proteins in the brain (Kopniczky et al, 2005). An antibody raised against the conserved transmembrane 3-4 linker region was used to recognize all AMPA receptor subunits (GluR1-GluR4 flip and flop) (Pickard et al, 2000).…”

Section: Sions Mglur7mentioning

confidence: 99%

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Concomitant Deficits in Working Memory and Fear Extinction Are Functionally Dissociated from Reduced Anxiety in Metabotropic Glutamate Receptor 7-Deficient Mice

Callaerts-Végh

Beckers

Ball

et al. 2006

Journal of Neuroscience

152

124

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Metabotropic glutamate receptor 7 (mGluR7), a receptor with a distinct brain distribution and a putative role in anxiety, emotional responding, and spatial working memory, could be an interesting therapeutic target for fear and anxiety disorders. mGluR7-deficient (mGluR7 Ϫ/Ϫ ) mice showed essentially normal performance in tests for neuromotor and exploratory activity and passive avoidance learning but prominent anxiolytic behavior in two anxiety tests. They showed a delayed learning curve during the acquisition of the hidden-platform water maze, and three interspersed probe trials indicated that mGluR7 Ϫ/Ϫ mice were slower to acquire spatial information. Working memory in the water maze task and the radial arm maze was impaired in mGluR7 Ϫ/Ϫ mice compared with mGluR7 ϩ/ϩ . mGluR7 Ϫ/Ϫ mice also displayed a higher resistance to extinction of fear-elicited response suppression in a conditioned emotional response protocol. In a non-fear-based water maze protocol, mGluR7 Ϫ/Ϫ mice displayed similar delayed extinction. These observed behavioral changes are probably not attributable to changes in AMPA or NMDA receptor function because expression levels of AMPA and NMDA receptors were unaltered. Extinction of conditioned fear is an active and context-dependent form of inhibitory learning and an experimental model for therapeutic fear reduction. It appears to depend on glutamatergic and higher-level brain functions similar to those involved in spatial working memory but functionally dissociated from those that mediate constitutional responses in anxiety tests.

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“…The dentate gyrus subfield of the hippocampus is particularly susceptible to seizures, and appears to be the primary locus of temporal lobe epilepsy. The vulnerability of the dentate gyrus to seizures may result from disrupted GABAergic synaptic transmission as the pathological changes that occur in the dentate during epilepsy include loss of GABAergic inhibitory interneurons [44][45][46] and sprouting of axons [47][48][49]. Synchronization, characteristic of epileptiform bursts, has been recorded in the hippocampus, and has been theorized to be mediated by electrical coupling via GJs [50].…”

Section: Introductionmentioning

confidence: 99%

Connexin-36 Knock-Out Mice have Increased Threshold for Kindled Seizures: Role of GABA Inhibition

Shin¹

2013

Biochem & Pharmacol

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Blockade of gap junctions (GJs) has been shown to reduce seizures in different epilepsy models. Gap junctionmediated, electrically-coupled neuronal networks have been implicated in neuronal synchronization, which is the hallmark of seizure activity. To further understand the role of GJs in seizures, in particular hippocampal seizures, we evaluated electrophysiological responses in the dentate gyrus subfield of the hippocampus, including GABA-mediated recurrent inhibition, seizuregenic stimulation, and seizure activity in response to perforant path kindling in Cx36 knockout (KO) mice compared to wild-type (WT) controls. In anesthetized mice, Cx36 KO mice were characterized by enhanced GABA-mediated recurrent inhibition. Stimulation of the perforant path at 10 Hz for 10 sec (i.e., 100 pulses) markedly enhanced population spike (PS) amplitudes and reduced paired-pulse GABA-mediated inhibition during the stimulation, induced an after discharge for approximately 10 sec at 7-10 sec into the stimulation, and suppressed PS amplitudes postictally for 5-10 min in both KO and WT mice. Repeated epochs of 10 Hz for 10 sec stimulation of the perforant path at 20 min intervals resulted in progressive and persistent disinhibition of paired-pulse responses in WT, but not KO mice. In freely-behaving seizure studies, stimulation of the perforant path (10 Hz for 10 sec) once/day resulted in progressive Stage I-IV seizures in both WT and KO mice. Once Stage IV was achieved, another Stage IV seizure could be elicited each day with the same behavioral response (i.e., Stage V). The threshold for kindled seizures was significantly greater in KO mice compared to WT controls for most stages of seizures. The Cx36 antagonist mefloquine (MFQ) and the typical anticonvulsant pentobarbital reduced Stage IV seizures in both WT and KO mice. Knock-out mice were more sensitive to the anti-epileptic effects of the typical anti-convulsant pentobarbital (20 mg/ kg). Taken together, these findings support the emerging view that reduction in GJ-mediated GABA electrical coupling reduces seizures, perhaps through enhancement of GABAergic feedback inhibition, which results from the uncoupling of the GABA recurrent interneurons from the resistive load that is inherent in their electrical connectivity.

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Lateral entorhinal cortex lesions rearrange afferents, glutamate receptors, increase seizure latency and suppress seizure‐induced c‐fosexpression in the hippocampus of adult rat

Cited by 27 publications

References 67 publications

Loss of Astrocytic Domain Organization in the Epileptic Brain

Loss of Astrocytic Domain Organization in the Epileptic Brain

Concomitant Deficits in Working Memory and Fear Extinction Are Functionally Dissociated from Reduced Anxiety in Metabotropic Glutamate Receptor 7-Deficient Mice

Connexin-36 Knock-Out Mice have Increased Threshold for Kindled Seizures: Role of GABA Inhibition

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