Search

The cerebral cortex integrates sensory information with emotional states and internal representations to produce coherent percepts, form associations, and execute voluntary actions. For the cortex to optimize perception, its neuronal network needs to dynamically retrieve and encode new information. Over the last few decades, research has started to provide insight into how the cortex serves these functions. Building on classical Hebbian plasticity models, the latest hypotheses hold that throughout experience and learning, streams of feedforward, feedback, and modulatory information operate in selective and coordinated manners to alter the strength of synapses and ultimately change the response properties of cortical neurons. Here, we describe cortical plasticity mechanisms that involve the concerted action of feedforward and long-range feedback input onto pyramidal neurons as well as the implication of local disinhibitory circuit motifs in this process.

Brain tissue slices are a common neuroscience model that allows relatively sophisticated analysis of neuronal networks in a simplified preparation. Most experimental methodology utilizes electrophysiological tools to probe these model systems. The work here demonstrates the adaptation of low-flow push-pull perfusion sampling (LFPS) to a brain slice system. LFPS is used to sample from the hippocampus of mouse brain slices. Perfusate amino acid levels are quantified following sampling with capillary electrophoresis. Glutamate was measured from the CA1 region of the hippocampus in slices taken from a cystine-glutamate transporter deletion mutant, xCT(-/-), and the background strain C57BL/6J. Sampling is performed over up to 6.5 h with standard tissue slice preparation and experimentation methods. Four amino acids were quantified to demonstrate the ability to perform LFPS and show good agreement with published literature. Perfusate glutamate levels are found to be significantly lower with xCT(-/-) slices (1.9(±0.5) μM) relative to controls (4.90(±1.1) μM). But, experiments with control slices show a significant decrease in glutamate over the 6 h sampling period that are not seen with xCT(-/-) slices. Increasing the LFPS sample collection rate during the first 90 min of sampling did not show a sampling artifact in perfusate glutamate content. Sampling immediately following slicing did not show an early increasing glutamate level that would be indicative of a significant contribution from blood or tissue damage. The data presented here show a complementarity to electrophysiological studies of tissue slices. The ability to characterize extracellular fluid chemical content with LFPS in these slices provides an alternative data stream for probing neurochemical signaling networks in brain tissue slices.

Most extracellular glutamate in the brain is released by xCT, a glial antiporter that exports glutamate and imports cystine. The function of xCT, and extracellular glutamate in general, remains unclear. Several lines of evidence suggest that glutamate from xCT could act in a paracrine fashion to suppress glutamatergic synapse strength by triggering removal of postsynaptic glutamate receptors. To test this idea, we used whole-cell patch-clamp electrophysiology and immunohistochemistry to quantify receptor number and synapse function in xCT knock-out mouse hippocampal CA3-CA1 synapses. Consistent with the hypothesis that xCT suppresses glutamate receptor number and synapse strength, xCT knock-out synapses showed increased AMPA receptor abundance with concomitant large enhancements of spontaneous and evoked synaptic transmission. We saw no evidence for changes in GABA receptor abundance or the overall number of glutamatergic synapses. The xCT knock-out phenotype was replicated by incubating slices in the xCT inhibitor (S)-4-carboxyphenylglycine, and consistent with the idea that xCT works by regulating extracellular glutamate, the xCT knock-out phenotype could be reproduced in controls by incubating the slices in glutamate-free aCSF. We conclude that glutamate secreted via xCT suppresses glutamatergic synapse strength by triggering removal of postsynaptic AMPA receptors.

We present a 48-year-old male with recurrent glioblastoma (GBM) who was enrolled in the NovoTTF-100A landmark phase III study and has been on device for >6 years. During this time, his magnetic resonance images demonstrated initial growth followed by a slow decrease in enhancement with continued residual disease. Long-term survivors in patients with recurrent GBM are rare, especially in the absence of definitive local treatment such as surgery or radiosurgery. We present the clinical, imaging and pathological findings for this patient in relation to use of the NovoTTF-100A device.

Background: This study compared the use of two commonly utilized dural closure techniques used in augmentation duraplasty for Chiari malformation I (CM I) and evaluated their efficacy and outcome in terms of quality of life assessments. Methods: This prospective randomized study compared sutureless (DuraGen) and suturable (Dura-Guard) techniques in CM I decompression. Clinical parameters, cost analysis, and SF-36 Quality of Life Questionnaire (QLQ) were utilized to assess outcome. Results: Thirty-four patients were enrolled. Average age was 38.7 ± 12.2 years (mean ± SD (Standard Deviation)) and 82% of patients were female. Sixteen patients received DuraGen and 18 Dura-Guard. Age and gender were similar among groups. Postoperative complications did not differ between groups. Operative cost and time were less for DuraGen, whereas hospital stay was less with Dura-Guard, neither was statistically significant. Average QLQ scores at months 1, 2, and 3 improved in both groups. Dura-Guard patients showed greater improvement in quality of life at month 2 (P < 0.05) but groups did not differ at final survey. All patient's physical health (P < 0.005) and function (P < 0.005) were significantly improved. Outcome did not differ between groups and all patients showed significant improvement (P < 0.05). Conclusion: Both techniques are effective in reaching the goals of decompressive surgery for CM I and did not differ in quality of life at final survey. All patients showed significant improvement in physical function, physical health, and outcome following surgery. With all variables being equal the choice of duraplasty material may be based upon surgeon's preference.