Selective Pharmacological Modulation of Pyramidal Neurons and Interneurons in the CA1 Region of the Rat Hippocampus.

The hippocampus is a complex network tightly regulated by interactions between excitatory and inhibitory neurons. In neurodegenerative disorders where cognitive functions such as learning and memory are impaired this excitation-inhibition balance may be altered. Interestingly, the uncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist memantine, currently in clinical use for the treatment of Alzheimer's disease, may alter the excitation-inhibition balance in the hippocampus.

Preconditioning induces tolerance by suppressing glutamate release in neuron culture ischemia models.

This study determined how preconditioned neurons responded to oxygen-glucose deprivation (OGD) to result in neuroprotection instead of neurotoxicity. Neurons preconditioned using chronically elevated synaptic activity displayed suppressed elevations in extracellular glutamate ([glutamateex ]) and intracellular Ca(2+) (Ca(2+) in ) during OGD. The glutamate uptake inhibitor TBOA induced neurotoxicity, but at a longer OGD duration for preconditioned cultures, suggestive of delayed up-regulation of transporter activity relative to non-preconditioned cultures.

A profile of the insulin receptor in cultured hippocampal slices.

Objectives: Insulin receptors (IRs) are distributed in a region-specific fashion throughout the brain, and may play a role in processes related to learning and memory. The hippocampus, which participates in spatial memory formation, is one region in which the IR is abundantly expressed. Organotypic hippocampal slice cultures (OHSCs) are an in vitro model that permits the easy manipulation of growth conditions, yet retains much of the source structure's cytoarchitecture.

From understanding cellular function to novel drug discovery: the role of planar patch-clamp array chip technology.

All excitable cell functions rely upon ion channels that are embedded in their plasma membrane. Perturbations of ion channel structure or function result in pathologies ranging from cardiac dysfunction to neurodegenerative disorders. Consequently, to understand the functions of excitable cells and to remedy their pathophysiology, it is important to understand the ion channel functions under various experimental conditions - including exposure to novel drug targets.

Choline-mediated depression of hippocampal synaptic transmission.

Choline is a micronutrient essential for the structural integrity of cellular membranes, and its presence at synapses follows either depolarization-induced pre-synaptic release or degradation of acetylcholine. Previous studies using whole-cell recording have shown that choline can modulate inhibitory input to hippocampal pyramidal neurons by acting upon nicotinic acetylcholine receptors (nAChRs) found on interneurons. However, little is known about how choline affects neuronal activity at the population level; therefore, we used extracellular recordings to assess its influence upon synaptic transmission in acutely prepared hippocampal slices.

Recordings of cultured neurons and synaptic activity using patch-clamp chips.

Planar patch-clamp chip technology has been developed to enhance the assessment of novel compounds for therapeutic efficacy and safety. However, this technology has been limited to recording ion channels expressed in isolated suspended cells, making the study of ion channel function in synaptic transmission impractical. Recently, we developed single- and dual-recording site planar patch-clamp chips and demonstrated their capacity to record ion channel activity from neurons established in culture.

Cellular distribution of the nicotinic acetylcholine receptor alpha7 subunit in rat hippocampus.

The hippocampus is a region of the mammalian brain that has been extensively studied due to its role in many forms of memory. To better understand hippocampal function, significant attention has focused upon the cellular distribution of ligand-gated ion channels. Despite strong cholinergic innervation from the basal forebrain and a dense expression of nicotinic acetylchoine receptors (nAChRs), the cellular distribution of subunits forming these receptors has received little attention.

Elevated synaptic activity preconditions neurons against an in vitro model of ischemia.

Tolerance to otherwise lethal cerebral ischemia in vivo or to oxygen-glucose deprivation (OGD) in vitro can be induced by prior transient exposure to N-methyl-D-aspartic acid (NMDA): preconditioning in this manner activates extrasynaptic and synaptic NMDA receptors and can require bringing neurons to the "brink of death." We considered if this stressful requirement could be minimized by the stimulation of primarily synaptic NMDA receptors. Subjecting cultured cortical neurons to prolonged elevations in electrical activity induced tolerance to OGD.

Synaptic activity and triphenyltetrazolium chloride metabolism are correlated after oxygen-glucose deprivation in acute, but not cultured, hippocampal slices.

The importance of the hippocampus to learning and memory has attracted significant attention to how the structure responds to damage. Although many studies have used either the acute hippocampal slice preparation or organotypic hippocampal slice cultures, little work has been done to determine if the choice of model is an important variable. The present study examined whether differences exist in how each model responds to a commonly studied ischemic-like paradigm, oxygen-glucose deprivation.

Cytoskeletal, synaptic, and nuclear protein changes associated with rat interface organotypic hippocampal slice culture development.

Although organotypic hippocampal slice cultures (OHSCs) are used to study function within the hippocampus, the effect of maintenance in vitro upon protein expression is not fully understood. Therefore, we examined developmental changes in cultures prepared from P8 rats and maintained on porous membranes between medium and atmosphere. Between 7 and 28 days following explantation, altered hippocampal morphology could not be detected despite a significant decrease in both MAP-2c and a mid-range tau isoform by 21 DIV.

Opposing effects of cyclooxygenase-2 selective inhibitors on oxygen-glucose deprivation-induced neurotoxicity.

Cyclooxygenase-2 inhibitors protect against excitotoxicity in vitro yet provide conflicting results in in vivo models of ischemia. To bridge the gap in understanding the discrepancies among these studies, the effects of different cyclooxygenase-2 inhibitors were studied in an in vitro model of ischemia. Oxygen-glucose deprivation (OGD) induced cyclooxygenase-2 protein expression in neuronal cortical cultures.