Hippocampal gabaergic inhibitory interneurons

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record In the hippocampus GABAergic local circuit inhibitory interneurons represent only ~10–15% of the total neuronal population; however, their remarkable anatomical and physiological diversity allows them to regulate virtually all aspects of cellular and circuit function. Here we provide an overview of the current state of the field of interneuron research, focusing largely on the hippocampus. We discuss recent advances related to the various cell types, including their development and maturation, expression of subtype-specific voltage-and ligand-gated channels, and their roles in network oscillations. We also discuss recent technological advances and approaches that have permitted high-resolution, subtype-specific examination of their roles in numerous neural circuit disorders and the emerging therapeutic strategies to ameliorate such pathophysiological conditions. The ultimate goal of this review is not only to provide a touchstone for the current state of the field, but to help pave the way for future research by highlighting where gaps in our knowledge exist and how a complete appreciation of their roles will aid in future therapeutic strategies.National Institute of Child Health and Human Developmen

Characteristics of the Mars Pathfinder Landing Site from CRISM Hyperspectral Imaging

Preliminary analysis of CRISM imaging of the Mars Pathfinder landing site is consistent with previously reported results from landed imaging. At tens of meters scale, the surface is largely dust-covered. Lee portions of topographic knobs are reddest and show most evidence for ferric mineralogy. The nearby 1.5-km diameter "Big Crater" exposes olivine, which is atypical of the northern plains. Big Crater may have penetrated northern plains material to expose buried basaltic highlands

Detection of TMPRSS2 : ERG fusion gene in circulating prostate cancer cells

Creative Commons Attribution-NonCommercial-Share Alike 3.0 license (CC BY-NC SA)Aim: To investigate the existence of TMPRSS2:ERG fusion gene in circulating tumor cells (CTC) from prostate cancer patients and its potential in monitoring tumor metastasis. Methods: We analyzed the frequency of TMPRSS2: ERG and TMPRSS2:ETV1 transcripts in 27 prostate cancer biopsies from prostatectomies, and TMPRSS2:ERG transcripts in CTC isolated from 15 patients with advanced androgen independent disease using reverse transcription polymerase chain reaction (RT-PCR). Fluorescence in situ hybridization (FISH) was applied to analyze the genomic truncation of ERG, which is the result of TMPRSS2:ERG fusion in 10 of the 15 CTC samples. Results: TMPRSS2: ERG transcripts were found in 44% of our samples, but we did not detect expression of TMPRSS2:ETV1. Using FISH analysis we detected chromosomal rearrangements affecting the ERG gene in 6 of 10 CTC samples, including 1 case with associated TMPRSS2:ERG fusion at the primary site. However, TMPRSS2:ERG transcripts were not detected in any of the 15 CTC samples, including the 10 cases analyzed by FISH. Conclusion: Although further study is required to address the association between TMPRSS2:ERG fusion and prostate cancer metastasis, detection of genomic truncation of the ERG gene by FISH analysis could be useful for monitoring the appearance of CTC and the potential for prostate cancer metastasis.Peer reviewedFinal Published versio

Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells.

This is the final version of the article. Available from Nature Publishing Group via the DOI in this record.Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction.Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.We thank Daniel Abebe for mouse colony maintenance and Kurt Auville for additional assistance with confocal imaging. We thank UNC Vector Core and Ed Boyden, MIT, Cambridge, MA, USA for generously providing AAV9-syn-Chrimson-TdTomato and AAV9-syn-Chronos-GFP. This work was supported by an intramural award to C.J.M. from the Eunice Kennedy–Shriver National Institute of Child Health and Human Development and a Competitive Fellowship Award to J.C.W. from the National Institute of Neurological Disorders and Strok

Presynaptic Kainate Receptor Activation Preserves Asynchronous GABA Release Despite the Reduction in Synchronous Release from Hippocampal Cholecystokinin Interneurons

Inhibitory synaptic transmission in the hippocampus in mediated by a wide variety of different interneuron classes which are assumed to play different roles in network activity. Activation of presynaptic kainate receptors (KARs) has been shown to reduce inhibitory transmission but the interneuron class(es) at which they act is only recently beginning to emerge. Using paired recordings we show that KAR activation causes a decrease in presynaptic release from CCK- but not PV-containing interneurons and that this decrease is observed when pyramidal cells, but not interneurons, are the postsynaptic target. We also show that although the synchronous release component is reduced, the barrage of asynchronous GABA release from CCK interneurons during sustained firing is unaffected by KAR activation. This indicates that presynaptic KARs preserve and act in concert with asynchronous release to switch CCK interneurons from a phasic inhibition mode to produce prolonged inhibition during periods of intense activity

Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Circuit computation requires precision in the timing, extent, and synchrony of principal cell (PC) firing that is largely enforced by parvalbumin-expressing, fast-spiking interneurons (PVFSIs). To reliably coordinate network activity, PVFSIs exhibit specialized synaptic and membrane properties that promote efficient afferent recruitment such as expression of high-conductance, rapidly gating, GluA4-containing AMPA receptors (AMPARs). We found that PVFSIs upregulate GluA4 during the second postnatal week coincident with increases in the AMPAR clustering proteins NPTX2 and NPTXR. Moreover, GluA4 is dramatically reduced in NPTX2(-/-)/NPTXR(-/-) mice with consequent reductions in PVFSI AMPAR function. Early postnatal NPTX2(-/-)/NPTXR(-/-) mice exhibit delayed circuit maturation with a prolonged critical period permissive for giant depolarizing potentials. Juvenile NPTX2(-/-)/NPTXR(-/-) mice display reduced feedforward inhibition yielding a circuit deficient in rhythmogenesis and prone to epileptiform discharges. Our findings demonstrate an essential role for NPTXs in controlling network dynamics highlighting potential therapeutic targets for disorders with inhibition/excitation imbalances such as schizophrenia.Work supported by a PRAT fellowship to M.S.W., an NICHD intramural award to C.J.M., NIDCD intramural research program funding to R.S.P., an NIMH intramural award to H.A.C., NIH grants (PAR-02-059, NS 039156) to P.F.W., and an NIH grant (EY022730) to M.T.

Gnome View: A tool for visual representation of human genome data

GnomeView is a tool for exploring data generated by the Human Gemone Project. GnomeView provides both graphical and textural styles of data presentation: employs an intuitive window-based graphical query interface: and integrates its underlying genome databases in such a way that the user can navigate smoothly across databases and between different levels of data. This paper describes GnomeView and discusses how it addresses various genome informatics issues

Measurement of cosmic-ray reconstruction efficiencies in the MicroBooNE LArTPC using a small external cosmic-ray counter

The MicroBooNE detector is a liquid argon time projection chamber at Fermilab designed to study short-baseline neutrino oscillations and neutrino-argon interaction cross-section. Due to its location near the surface, a good understanding of cosmic muons as a source of backgrounds is of fundamental importance for the experiment. We present a method of using an external 0.5 m (L) x 0.5 m (W) muon counter stack, installed above the main detector, to determine the cosmic-ray reconstruction efficiency in MicroBooNE. Data are acquired with this external muon counter stack placed in three different positions, corresponding to cosmic rays intersecting different parts of the detector. The data reconstruction efficiency of tracks in the detector is found to be $\epsilon_{\mathrm{data}}=(97.1\pm0.1~(\mathrm{stat}) \pm 1.4~(\mathrm{sys}))\%$, in good agreement with the Monte Carlo reconstruction efficiency $\epsilon_{\mathrm{MC}} = (97.4\pm0.1)\%$. This analysis represents a small-scale demonstration of the method that can be used with future data coming from a recently installed cosmic-ray tagger system, which will be able to tag $\approx80\%$ of the cosmic rays passing through the MicroBooNE detector.Comment: 19 pages, 12 figure