Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures

Background  

Excitotoxicity occurs in a number of pathogenic states including stroke and epilepsy. The adaptations of neuronal circuits in response to such insults may be expected to play an underlying role in pathogenesis. Synchronous neuronal firing can be induced in isolated hippocampal slices and involves all regions of this structure, thereby providing a measure of circuit activity. The effect of an excitotoxic insult (kainic acid, KA) on Mg²⁺-free-induced synchronized neuronal firing was tested in organotypic hippocampal culture by measuring extracellular field activity in CA1 and CA3.     

Ontogeny of ATP hydrolysis and isoform expression of the Plasma Membrane Ca2+-ATPase in mouse brain

Background  

Plasma membrane Ca²⁺-ATPases (PMCAs) are high affinity Ca²⁺ transporters actively involved in intracellular Ca²⁺ homeostasis. Considering the critical role of Ca²⁺ signalling in neuronal development and plasticity, we have analyzed PMCA-mediated Ca²⁺-ATPase activity and PMCA-isoform content in membranes from mouse cortex, hippocampus and cerebellum during postnatal development.     

Estrogen protects neuronal cells from amyloid beta-induced apoptosis via regulation of mitochondrial proteins and function

Background  

Neurodegeneration in Alzheimer's disease is associated with increased apoptosis and parallels increased levels of amyloid beta, which can induce neuronal apoptosis. Estrogen exposure prior to neurotoxic insult of hippocampal neurons promotes neuronal defence and survival against neurodegenerative insults including amyloid beta. Although all underlying molecular mechanisms of amyloid beta neurotoxicity remain undetermined, mitochondrial dysfunction, including altered calcium homeostasis and Bcl-2 expression, are involved in neurodegenerative vulnerability.     

Increased spinal prodynorphin gene expression in reinflammation-associated hyperalgesia after neonatal inflammatory insult

Background  

Neuroplasticity induced by neonatal inflammation is the consequence of a combination of activity-dependent changes in neurons. We investigated neuronal sensitivity to a noxious stimulus in a rat model of neonatal hind-paw peripheral inflammation and assessed changes in pain behaviour at the physiological and molecular levels after peripheral reinflammation in adulthood.     

Convulsant bicuculline modifies CNS muscarinic receptor affinity

Background  

Previous work from this laboratory has shown that the administration of the convulsant drug 3-mercaptopropionic acid (MP), a GAD inhibitor, modifies not only GABA synthesis but also binding of the antagonist [³H]-quinuclidinyl benzilate ([³H]-QNB) to central muscarinic receptors, an effect due to an increase in affinity without modifications in binding site number. The cholinergic system has been implicated in several experimental epilepsy models and the ability of acetylcholine to regulate neuronal excitability in the neocortex is well known. To study the potential relationship between GABAergic and cholinergic systems with seizure activity, we analyzed the muscarinic receptor after inducing seizure by bicuculline (BIC), known to antagonize the GABA-A postsynaptic receptor subtype.     

Human in vitro reporter model of neuronal development and early differentiation processes

Background  

During developmental and adult neurogenesis, doublecortin is an early neuronal marker expressed when neural stem cells assume a neuronal cell fate. To understand mechanisms involved in early processes of neuronal fate decision, we investigated cell lines for their capacity to induce expression of doublecortin upon neuronal differentiation and develop in vitro reporter models using doublecortin promoter sequences.     

LV-pIN-KDEL: a novel lentiviral vector demonstrates the morphology,dynamics and continuity of the endoplasmic reticulum in live neurones

Background  

The neuronal endoplasmic reticulum (ER) is an extensive, complex endomembrane system, containing Ca²⁺ pumps, and Ca²⁺ channels that permit it to act as a dynamic calcium store. Currently, there is controversy over the continuity of the ER in neurones, how this intersects with calcium signalling and the possibility of physical compartmentalisation. Unfortunately, available probes of ER structure such as vital dyes are limited by their membrane specificity. The introduction of ER-targeted GFP plasmids has been a considerable step forward, but these are difficult to express in neurones through conventional transfection approaches. To circumvent such problems we have engineered a novel ER-targeted GFP construct, termed pIN-KDEL, into a 3^rd generation replication-defective, self-inactivating lentiviral vector system capable of mediating gene transduction in diverse dividing and post-mitotic mammalian cells, including neurones.     

Newly generated cells are increased in hippocampus of adult mice lacking a serine protease inhibitor

Background  

Neurogenesis in the hippocampal dentate gyrus and the subventricular zone occurs throughout the life of mammals and newly generated neurons can integrate functionally into established neuronal circuits. Neurogenesis levels in the dentate gyrus are modulated by changes in the environment (enrichment, exercise), hippocampal-dependent tasks, NMDA receptor (NMDAR) activity, sonic hedgehog (SHH) and/or other factors.     

Neuron participation in a synchrony-encoding assembly

Background  

Synchronization of action potentials between neurons is considered to be an encoding process that allows the grouping of various and multiple features of an image leading to a coherent perception. How this coding neuronal assembly is configured is debated. We have previously shown that the magnitude of synchronization between excited neurons is stimulus-dependent. In the present investigation we compare the levels of synchronization between synchronizing individual neurons and the synchronizing pool of cells to which they belong.     

Signaling involved in neurite outgrowth of postnatally born subventricular zone neurons in vitro

Background  

Neurite outgrowth is a key process during neuronal migration and differentiation. Complex intracellular signaling is involved in the initiation of neurite protrusion and subsequent elongation. Although, in general many constituents of the machinery involved in this multi-stage process are common for neurons in distinct brain areas, there are notable differences between specific neuronal subtypes.     

GT1b-induced neurotoxicity is mediated by the Akt/GSK-3/tau signaling pathway but not caspase-3 in mesencephalic dopaminergic neurons

Background  

Gangliosides, sialic acid-containing glycosphingolipids exist in mammalian cell membranes particularly neuronal membranes. The trisialoganglioside (GT1b) is one of the major brain gangliosides and acts as an endogenous regulator in the brain. We previously showed GT1b induces mesencephalic dopaminergic (DA) neuronal death, both in vivo and in vitro. We further investigate the underlying mechanisms of GT1b neurotoxicity.     

A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis

Background  

The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization.     

Functional effects of spinocerebellar ataxia type 13 mutations are conserved in zebrafish Kv3.3 channels

Background  

The zebrafish has been suggested as a model system for studying human diseases that affect nervous system function and motor output. However, few of the ion channels that control neuronal activity in zebrafish have been characterized. Here, we have identified zebrafish orthologs of voltage-dependent Kv3 (KCNC) K⁺ channels. Kv3 channels have specialized gating properties that facilitate high-frequency, repetitive firing in fast-spiking neurons. Mutations in human Kv3.3 cause spinocerebellar ataxia type 13 (SCA13), an autosomal dominant genetic disease that exists in distinct neurodevelopmental and neurodegenerative forms. To assess the potential usefulness of the zebrafish as a model system for SCA13, we have characterized the functional properties of zebrafish Kv3.3 channels with and without mutations analogous to those that cause SCA13.     

Activation profiles of opioid ligands in HEK cells expressing δ opioid receptors

Background  

The aim of the present study was to characterize the activation profiles of 15 opioid ligands in transfected human embryonic kidney cells expressing only δ opioid receptors. Activation profiles of most of these ligands at δ opioid receptors had not been previously characterized in vitro. Receptor activation was assessed by measuring the inhibition of forskolin-stimulated cAMP production.     

Calcium-sensitive regulation of monoamine oxidase-A contributes to the production of peroxyradicals in hippocampal cultures: implications for Alzheimer disease-related pathology

Background  

Calcium (Ca²⁺) has recently been shown to selectively increase the activity of monoamine oxidase-A (MAO-A), a mitochondria-bound enzyme that generates peroxyradicals as a natural by-product of the deamination of neurotransmitters such as serotonin. It has also been suggested that increased intracellular free Ca²⁺ levels as well as MAO-A may be contributing to the oxidative stress associated with Alzheimer disease (AD).     

Coding of shape from shading in area V4 of the macaque monkey

Background  

The shading of an object provides an important cue for recognition, especially for determining its 3D shape. However, neuronal mechanisms that allow the recovery of 3D shape from shading are poorly understood. The aim of our study was to determine the neuronal basis of 3D shape from shading coding in area V4 of the awake macaque monkey.