Distinct P2Y Receptors Mediate Extension and Retraction of Microglial Processes in Epileptic and Peritumoral Human Tissue.

Microglia exhibit multiple, phenotype-dependent motility patterns often triggered by purinergic stimuli. However, little data exist on motility of human microglia in pathological situations. Here we examine motility of microglia stained with a fluorescent lectin in tissue slices from female and male epileptic patients diagnosed with mesial temporal lobe epilepsy or cortical glioma (peritumoral cortex).

Lipid markers and related transcripts during excitotoxic neurodegeneration in kainate-treated mice.

Lipid homeostasis is dysregulated in some neurodegenerative diseases and after brain injuries due to excess glutamate or lack of oxygen. However the kinetics and cell specificity of dysregulation in different groups of lipids during excitotoxic neuronal death are not clear. Here we examined the changes during excitotoxic neuronal death induced by injecting kainic acid (KA) into the CA1 region of mouse hippocampus.

Microglial phenotypes in the human epileptic temporal lobe.

Microglia, the immune cells of the brain, are highly plastic and possess multiple functional phenotypes. Differences in phenotype in different regions and different states of epileptic human brain have been little studied. Here we use transcriptomics, anatomy, imaging of living cells and ELISA measurements of cytokine release to examine microglia from patients with temporal lobe epilepsies.

New role of P2X7 receptor in an Alzheimer's disease mouse model.

Extracellular aggregates of amyloid β (Aβ) peptides, which are characteristic of Alzheimer's disease (AD), act as an essential trigger for glial cell activation and the release of ATP, leading to the stimulation of purinergic receptors, especially the P2X7 receptor (P2X7R). However, the involvement of P2X7R in the development of AD is still ill-defined regarding the dual properties of this receptor. Particularly, P2X7R activates the NLRP3 inflammasome leading to the release of the pro-inflammatory cytokine, IL-1β; however, P2X7R also induces cleavage of the amyloid precursor protein generating Aβ peptides or the neuroprotective fragment sAPPα.

Imaging pathological activities of human brain tissue in organotypic culture.

Background: Insights into human brain diseases may emerge from tissue obtained after operations on patients. However techniques requiring transduction of transgenes carried by viral vectors cannot be applied to acute human tissue.

New Method: We show that organotypic culture techniques can be used to maintain tissue from patients with three different neurological syndromes for several weeks in vitro.

Induction of Anti-Hebbian LTP in CA1 Stratum Oriens Interneurons: Interactions between Group I Metabotropic Glutamate Receptors and M1 Muscarinic Receptors.

Unlabelled: An anti-Hebbian form of LTP is observed at excitatory synapses made with some hippocampal interneurons. LTP induction is facilitated when postsynaptic interneurons are hyperpolarized, presumably because Ca(2+) entry through Ca(2+)-permeable glutamate receptors is enhanced. The contribution of modulatory transmitters to anti-Hebbian LTP induction remains to be established.

Increasing the effectiveness of intracerebral injections in adult and neonatal mice: a neurosurgical point of view.

Intracerebral injections of tracers or viral constructs in rodents are now commonly used in the neurosciences and must be executed perfectly. The purpose of this article is to update existing protocols for intracerebral injections in adult and neonatal mice. Our procedure for stereotaxic injections in adult mice allows the investigator to improve the effectiveness and safety, and save time.

An organotypic brain slice preparation from adult patients with temporal lobe epilepsy.

Background: A long-term in vitro preparation of diseased brain tissue would facilitate work on human pathologies. Organotypic tissue cultures retain an appropriate neuronal form, spatial arrangement, connectivity and electrical activity over several weeks. However, they are typically prepared with tissue from immature animals.

Recurrent synapses and circuits in the CA3 region of the hippocampus: an associative network.

In the CA3 region of the hippocampus, pyramidal cells excite other pyramidal cells and interneurons. The axons of CA3 pyramidal cells spread throughout most of the region to form an associative network. These connections were first drawn by Cajal and Lorente de No.

The paradox of the paroxysm: can seizure precipitants help explain human ictogenesis?

An epileptic brain is permanently in a diseased state, but seizures occur rarely and without warning. Here we examine this paradox, common to paroxysmal diseases. We review the problem in the context of the prototypic acquired epilepsies of the medial temporal lobe.

Group I mGluR agonist-evoked long-term potentiation in hippocampal oriens interneurons.

Several subtypes of interneurons in the feedback circuit in stratum oriens of the hippocampus exhibit NMDA receptor-independent long-term potentiation (LTP) at glutamatergic synapses made by local pyramidal neurons. LTP has been reported with both "Hebbian" and "anti-Hebbian" induction protocols, where high-frequency presynaptic stimulation is paired with either postsynaptic depolarization or hyperpolarization. Do these phenomena represent distinct forms of plasticity, dependent on group I metabotropic receptors (mGluRs) and rectifying Ca2+ -permeable AMPA receptors, respectively? Blockade of either mGluR1 or mGluR5 prevented anti-Hebbian LTP induction in stratum oriens interneurons in rat hippocampal slices.

Short- and long-term depression at glutamatergic synapses on hippocampal interneurons by group I mGluR activation.

Group I metabotropic glutamate receptors (mGluRs) are expressed by many interneurons of the hippocampus. Although they have been implicated in short- and long-term synaptic plasticity of glutamatergic transmission, their roles in modulating transmission to interneurons are incompletely understood. The selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) acutely depressed transmission at synapses in the feed-forward inhibitory pathway made by Schaffer collaterals on interneurons in the rat hippocampal CA1 sub-field.

Gene expression analysis of the emergence of epileptiform activity after focal injection of kainic acid into mouse hippocampus.

We report gene profiling data on genomic processes underlying the progression towards recurrent seizures after injection of kainic acid (KA) into the mouse hippocampus. Focal injection enabled us to separate the effects of proepileptic stimuli initiated by KA injection. Both the injected and contralateral hippocampus participated in the status epilepticus.

Epileptiform activities in slices of hippocampus from mice after intra-hippocampal injection of kainic acid.

Intra-hippocampal kainate injection induces the emergence of recurrent seizures after a delay of 3-4 weeks. We examined the cellular and synaptic basis of this activity in vitro using extracellular and intracellular records from longitudinal hippocampal slices. These slices permitted recordings from the dentate gyrus, the CA3 and CA1 regions and the subiculum of both the injected and the contralateral non-injected hippocampus.

Effects of focal injection of kainic acid into the mouse hippocampus in vitro and ex vivo.

Intra-hippocampal kainate injection induces an epileptiform activity termed status epilepticus. We examined the emergence of this activity with extracellular and intracellular records of responses (1) to focal kainate (KA) application in slices of mouse hippocampus and (2) of slices from mice injected with KA. The effects varied with distance from the injection site of KA.

Mesial temporal lobe epilepsy: a pathological replay of developmental mechanisms?

Focal epilepsies of the mesial temporal lobe are often associated with a hippocampal sclerosis. Changes in Cl homeostasis and GABAergic signalling in downstream regions, may contribute to the human pathology. A review of changes in cellular and synaptic function and connectivity after de-afferentation suggests this epileptic syndrome may involve a pathological replay of developmental mechanisms.