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The investigation of brain networks and neural circuits involves the crucial aspects of observing and modulating neurophysiological activity. Recently, opto-electrodes have emerged as an efficient tool for electrophysiological recording and optogenetic stimulation, which has greatly facilitated the analysis of neural coding. However, implantation and electrode weight control have posed significant challenges in achieving long-term and multi-regional brain recording and stimulation. To address this issue, we have developed a mold and custom-printed circuit board-based opto-electrode. We report successful optoelectrode placement and high-quality electrophysiological recordings from the default mode network (DMN) of the mouse brain. This novel opto-electrode facilitates synchronous recording and stimulation in multiple brain regions and holds promise for advancing future research on neural circuits and networks. [ABSTRACT FROM AUTHOR]

Large size monolayer Molybdenum disulphide (MoS2) was successfully grown by chemical vapor deposition method under an atmospheric pressure. The electrical transport properties of the fabricated back-gate monolayer MoS2 field effect transistors (FETs) were investigated under low temperatures; a peak field effect mobility of 59 cm2V–1s–1 was achieved. With the assist of Raman measurement under low temperature, this work identified the mobility limiting factor for the monolayer MoS2 FETs: homopolar phonon scattering under low temperature and electron-polar optical phonon scattering at room temperature. [ABSTRACT FROM AUTHOR]

Stroke activates microglia pro-inflammatory response that not only induces the early neuronal injuries but also causes the secondary brain infarction. Yet, the underlying mechanisms for how microglia become activated in stroke are still unknown. Here, using the next-generation of RNA sequencing we find a total of 778 genes increasingly expressed in brain of stroke mice. Of these, we identified Hmgb2 as a microglia proinflammatory mediator by promoting the transcription of Ctss. Inhibition of either Hmgb2 or Ctss blocks microglia pro-inflammatory response and protects against brain damages and improves the neurological functions of stroke mice. This study uncovers Hmgb2 and Ctss as the major microglia inflammatory response mediators in stroke and hence warrants the promising targets for stroke therapies. [ABSTRACT FROM AUTHOR]

The aberrant activation of CDK5 has been implicated in neuronal death in stroke. The goal of this study is to determine whether knocking down CDK5 by a peptide-directed lysosomal degradation approach is therapeutically effective against stroke. We synthesized a membrane-permeable peptide that specifically binds to CDK5 with a chaperone-mediated autophagy targeting motif (Tat-CDK5-CTM) and tested its therapeutic effects on a mouse model of ischemic stroke. Our results showed that Tat-CDK5-CTM blocked the CDK5-NR2B interaction, resulting in the degradation of CDK5, which in turn prevented calcium overload and neuronal death in cultured neurons. Tat-CDK5-CTM also reduced the infarction area and neuronal loss and improved the neurological functions in MCAO (Middle cerebral artery occlusion) mice. The peptide-directed lysosomal degradation of CDK5 is a promising therapeutic intervention for stroke. [ABSTRACT FROM AUTHOR]

ZnO microrods (whiskers) were fabricated by a simple thermal oxidation method. The morphologies of the samples were detected by the scanning electron microscope, which showed the ZnO microrods were about 30 μm long with a diameter of 1–2 μm. In the photoluminescence (PL) spectra, only the exciton related emission bands in the ultraviolet region could be obtained at room temperature. And, a new emission band due to the exciton–exciton collision process was observed at the low energy side of the free exciton emission under the excitation intensity of 2.1 kW/cm[sup 2]. This emission band increased nonlinearly. When the excitation intensity was increased above 16 kW/cm[sup 2] some fine structures could also be seen clearly in the PL spectra. These fine structures originated from the cavity modes of the Fabry–Pérot étalon. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities. Guided by the structural data, we developed potent non-phosphorylated GK inhibitory peptides capable of blocking the PSD-95/SAPAP interaction and interfering with PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are genetically encodable for investigating the functions of the PSD-95/SAPAP interaction in vivo. [ABSTRACT FROM AUTHOR]

Choline acetyltransferase neurons in the vertical diagonal band of Broca (vChATs) degenerate in the early stage of Alzheimer's disease (AD). Here, we report that vChATs directly innervate newly generated immature neurons (NGIs) in the dorsal hippocampus (dNGIs) of adult mice and regulate both the dNGIs survival and spatial pattern separation. In a mouse model that exhibits amyloid-β plaques similar to AD patients, cholinergic synaptic transmission, dNGI survival and spatial pattern separation are impaired. Activation of vChATs with theta burst stimulation (TBS) that alleviates the decay in cholinergic synaptic transmission effectively protects against spatial pattern separation impairments in the AD mice and this protection was completely abolished by inhibiting the dNGIs survival. Thus, the impairments of pattern separation-associated spatial memory in AD mice are in part caused by degeneration of cholinergic synaptic transmission that modulates the dNGIs survival. [ABSTRACT FROM AUTHOR]

This paper reported AlGaN/GaN high electron mobility transistors (HEMTs) with low sub-threshold swing SS on free-standing GaN wafer. High quality AlGaN/GaN epi-layer has been grown by metal-organic chemical vapor deposition (MOCVD) on free-standing GaN, small full-width hall maximum (FWHM) of 42.9 arcsec for (0002) GaN XRD peaks and ultralow dislocation ~104-105 cm-2) were obtained. Due to these extremely high quality material properties, the fabricated AlGaN/GaN HEMTs achieve a low SS ( ~60 mV/decade), low hysteresis of 54 mV, and high peak electron mobility μeff of ~1456 cm2V-1s-1. Systematic study of materials properties and device characteristics exhibits that GaN-on-GaN AlGaN/GaNHEMTs are promising candidate for next generation high power device applications. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex virus type 1 strain 129 (H129) has represented a promising anterograde neuronal circuit tracing tool, which complements the existing retrograde tracers. However, the current H129 derived tracers are multisynaptic, neither bright enough to label the details of neurons nor capable of determining direct projection targets as monosynaptic tracer. Methods: Based on the bacterial artificial chromosome of H129, we have generated a serial of recombinant viruses for neuronal circuit tracing. Among them, H129-G4 was obtained by inserting binary tandemly connected GFP cassettes into the H129 genome, and H129-ΔTK-tdT was obtained by deleting the thymidine kinase (TK) gene and adding tdTomato coding gene to the H129 genome. Then the obtained viral tracers were tested in vitro and in vivo for the tracing capacity. Results: H129-G4 is capable of transmitting through multiple synapses, labeling the neurons by green florescent protein, and visualizing the morphological details of the labeled neurons. H129-ΔTK-tdT neither replicates nor spreads in neurons alone, but transmits to and labels the postsynaptic neurons with tdTomato in the presence of complementary expressed TK from a helper virus. H129-ΔTK-tdT is also capable to map the direct projectome of the specific neuron type in the given brain regions in Cre transgenic mice. In the tested brain regions where circuits are well known, the H129-ΔTK-tdT tracing patterns are consistent with the previous results. Conclusions: With the assistance of the helper virus complimentarily expressing TK, H129-ΔTK-tdT replicates in the initially infected neuron, transmits anterogradely through one synapse, and labeled the postsynaptic neurons with tdTomato. The H129-ΔTK-tdT anterograde monosynaptic tracing system offers a useful tool for mapping the direct output in neuronal circuitry. H129-G4 is an anterograde multisynaptic tracer with a labeling signal strong enough to display the details of neuron morphology. [ABSTRACT FROM AUTHOR]

Exchange protein directly activated by cAMP (Epac) is a direct effector for the ubiquitous second messenger cAMP. Epac activates the phospholipase Cε (PLCε) pathway. PLCβ has been linked to the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Here, we report that Epac facilitates endocannabinoid-mediated retrograde synaptic depression through activation of PLCε. Intracellular loading of a selective Epac agonist 8-CPT-2Me-cAMP into ventral tegmental area (VTA) dopamine neurons enabled previously ineffective stimuli to induce depolarization-induced suppression of inhibition (DSI) and long-term depression of IPSCs (I-LTD) in the VTA. DSI and I-LTD are mediated by 2-AG since they were blocked by a diacylglycerol lipase inhibitor. The effects of 8-CPT-2Me-cAMP on DSI and I-LTD were absent in Epac2 and PLCε knock-out mice, but remained intact in Epac1 knock-out mice. These results identify a novel mechanism for on-demand synthesis of retrograde signaling 2-AG by the Epac2-PLCε pathway. We investigated the functional significance of Epac2-PLCε-2-AG signaling in regulating inhibitory synaptic plasticity in VTA dopamine neurons induced by in vivo cocaine exposure. We showed that cocaine place conditioning led to a decrease in the frequency and amplitude of spontaneous IPSCs and an increase in action potential firing in wild-type mice, but not in Epac2 or PLCε knock-out mice. Together, these results indicate that the Epac2-PLCε-2-AG signaling cascade contributes to cocaine-induced disinhibition of VTA dopamine neurons. [ABSTRACT FROM AUTHOR]

The over-production of β-amyloid (Aβ) has been strongly correlated to neuronal dysfunction and altered synaptic plasticity in Alzheimer's disease (AD). Accordingly, it has been proposed that disrupted synaptic transmission and neuronal network instability underlie memory failure that is evident in the early phases of AD. Homeostatic synaptic plasticity (HSP) serves to restrain neuronal activity within a physiological range. Therefore a disruption of this mechanism may lead to destabilization in synaptic and neural circuit function. Here, we report that during HSP by neuronal activity deprivation, application of Aβ results in an aberrant over-response of the up-regulation of AMPA receptor (AMPAR)-mediated synaptic currents and cell-surface AMPAR expression. In the visual cortex, in vivo HSP induced by visual deprivation shows a similar over-response following an Aβ local injection. Aβ increases the expression of GluA2-lacking, calcium permeable AMPARs (CP-AMPARs), which are required for the initiation, but not maintenance of HSP. Both GluA2-lacking and GluA2-containing AMPARs contribute to the Aβ-mediated over-scaling of HSP. We also find that Aβ induces the dissociation of HDAC1 from the miR124 transcription factor EVI1, leading to an up-regulation of miR124 expression and increased amount of CP-AMPARs. Thus, via aberrant stimulation of miR124 expression and biogenesis of CP-AMPARs, Aβ is able to induce an over response in HSP. This Aβ-mediated dysregulation in homeostatic plasticity may play an important role in the pathogenesis of altered neural function and memory deficits in the early stages of AD. [ABSTRACT FROM AUTHOR]

Excitatory pyramidal neurons in the entorhinal cortical layer II region (ECIIPN) form functional excitatory synapses with CA1 parvalbumin inhibitory neurons (CA1PV) and undergo selective degeneration in the early stages of Alzheimer's disease (AD). Here, we show that death-associated protein kinase 1 (DAPK1) is selectively activated in ECIIPN of AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN-CA1PV synaptic loss and improves spatial learning and memory in AD mice. This study demonstrates that activation of DAPK1 in ECIIPN contributes to a memory loss in AD and hence warrants a promising target for the treatment of AD. [ABSTRACT FROM AUTHOR]

The energy band alignment between ZnO and multilayer (ML)-MoS2 was characterized using high-resolution x-ray photoelectron spectroscopy. The ZnO film was deposited using an atomic layer deposition tool, and ML-MoS2 was grown by chemical vapor deposition. A valence band offset (VBO) of 3.32 eV and a conduction band offset (CBO) of 1.12eV were obtained for the ZnO/ ML-MoS2 interface without any treatment. With CHF3 plasma treatment, a VBO and a CBO across the ZnO/ML-MoS2 interface were found to be 3.54 eV and 1.34 eV, respectively. With the CHF3 plasma treatment, the band alignment of the ZnO/ML-MoS2 interface has been changed from type II or staggered band alignment to type III or misaligned one, which favors the electron-hole pair separation. The band alignment difference is believed to be dominated by the down-shift in the core level of Zn 2p or the interface dipoles, which is caused by the interfacial layer rich in F. [ABSTRACT FROM AUTHOR]

Exchange protein directly activated by cAMP (Epac) and protein kinase A (PKA) are intracellular receptors for cAMP. Although PKA and its downstream effectors have been studied extensively in the context of drug addiction, whether and how Epac regulates cellular and behavioral effects of drugs of abuse remain essentially unknown. Epac is known to regulate AMPA receptor (AMPAR) trafficking. Previous studies have shown that a single cocaine exposure in vivo leads to an increase in GluA2-lacking AMPARs in dopamine neurons of the ventral tegmental area (VTA). We tested the hypothesis that Epac mediates cocaine-induced changes in AMPAR subunit composition in the VTA. We report that a single cocaine injection in vivo in wild-type mice leads to inward rectification of EPSCs and renders EPSCs sensitive to a GluA2-lackingAMPARblocker in VTA dopamine neurons. The cocaine-induced increase in GluA2-lacking AMPARs was absent in Epac2-deficient mice but not in Epac1-deficient mice. In addition, activation of Epac with the selective Epac agonist 8-CPT-2Me-cAMP (8-CPT) recapitulated the cocaine-induced increase in GluA2-lackingAMPARs, and the effects of 8-CPT were mediated by Epac2. We also show that conditioned place preference to cocaine was impaired in Epac2-deficient mice and in mice in which Epac2 was knocked down in the VTA but was not significantly altered in Epac1-deficient mice. Together, these results suggest that Epac2 is critically involved in the cocaine-induced change in AMPAR subunit composition and drug-cue associative learning. [ABSTRACT FROM AUTHOR]

The energy band alignment between HfO2/multilayer (ML)-MoS2 was characterized using high-resolution x-ray photoelectron spectroscopy. The HfO2 was deposited using an atomic layer deposition tool, and ML-MoS2 was grown by chemical vapor deposition. A valence band offset (VBO) of 1.98 eV and a conduction band offset (CBO) of 2.72 eV were obtained for the HfO2/ML-MoS2 interface without any treatment. With CHF3 plasma treatment, a VBO and a CBO across the HfO2/ML-MoS2 interface were found to be 2.47 eV and 2.23 eV, respectively. The band alignment difference is believed to be dominated by the down-shift in the core level of Hf 4d and up-shift in the core level of Mo 3d, or the interface dipoles, which caused by the interfacial layer in rich of F. [ABSTRACT FROM AUTHOR]

Necrosis and apoptosis are two distinct types of mechanisms that mediate ischemic injury. But a signaling point of convergence between them has yet to be identified. Here, we show that activated death-associated protein kinase 1 (DAPK1), phosphorylates p53 at serine-23 (pS23) via a direct binding of DAPK1 death domain (DAPK1DD) to the DNA binding motif of p53 (p53DM). We uncover that the pS23 acts as a functional version of p53 and mediates necrotic and apoptotic neuronal death; in the nucleus, pS23 induces the expression of proapoptotic genes, such as Bax, whereas in the mitochondrial matrix, pS23 triggers necrosis via interaction with cyclophilin D (CypD) in cultured cortical neurons from mice. Deletion of DAPK1DD (DAPK1DDΔ) or application of Tat-p53DM that interrupts DAPK1-p53 interaction blocks these dual pathways of pS23 actions in mouse cortical neurons. Thus, the DAPK1-p53 interaction is a signaling point of convergence of necrotic and apoptotic pathways and is a desirable target for the treatment of ischemic insults. [ABSTRACT FROM AUTHOR]

EPAC (Exchange Proteins Activated by cAMP) regulates glutamate transmitter release in the central neurons, but a role underlying this regulation has yet to be identified. Here we show that EPAC binds directly to the intracellular loop of an ATP-sensitive potassium (KATP) channel type-1 sulfonylurea receptor (SUR1) receptor consisting of amino acids 859 - 881 (SUR1 859-881). Ablation of EPAC or expression of SUR1 859-881, which intercepts EPAC-SUR1 binding, increases the open probability of KATP channels consisting of the Kir6.1 subunit and SUR1. Opening of KATP channels inhibits glutamate release and reduces seizure vulnerability in adult mice. Therefore, EPAC inter-action with SUR1 controls seizure susceptibility and possibly acts via regulation of glutamate release. [ABSTRACT FROM AUTHOR]

The Kir6.1 channels are a subtype of ATP-sensitive inwardly rectifying potassium (KATP) channels that play an essential role in coupling the cell’s metabolic events to electrical activity. In this study, we show that functional Kir6.1 channels are located at excitatory pre-synaptic terminals as a complex with type-1 Sulfonylurea receptors (SUR1) in the hippocampus. The mutant mice with deficiencies in expressing the Kir6.1 or the SUR1 gene are more vulnerable to generation of epileptic form of seizures, compared to wild-type controls. Whole-cell patch clamp recordings demonstrate that genetic deletion of the Kir6.1/SUR1 channels enhances glutamate release at CA3 synapses. Hence, expression of functional Kir6.1/SUR1 channels inhibits seizure responses and possibly acts via limiting excitatory glutamate release. [ABSTRACT FROM AUTHOR]

ATP-sensitive K+ (KATP) channels that are gated by intracellular ATP/ADP concentrations are a unique subtype of potassium channels and play an essential role in coupling intracellular metabolic events to electrical activity. Opening of KATP channels during energy deficits in the CNS induces efflux of potassium ions and in turn hyperpolarizes neurons. Thus, activation of KATP channels is thought to be able to counteract excitatory insults and protect against neuronal death. In this review, we bring together recent studies about what kinds of molecules are needed to build and regulate arrays of KATP channel functions in the CNS neurons. We propose a model to explain how KATP channel activation regulates glutamate release from the pre-synaptic terminals and how this regulation protects against ischemic neuronal injury and epilepsy. [ABSTRACT FROM AUTHOR]

FeSe films have been grown on GaAs (001) substrates by low-pressure metal organic vapor deposition at different temperatures. X-ray diffraction analysis indicated that the FeSe films grown at substrate temperatures (Ts) between 220 and 340 °C were preferentially oriented with tetragonal structure. It was not possible to deposit films at Ts above 400 °C. The atomic molar ratios of Se/Fe increased with increasing the flow rate of H2Se/Fe(CO)5 and the growth temperature. The electronic property results showed that the conductive type of FeSe could be adjusted by controlling the growth temperature. The coercivity of FeSe decreased with increasing the growth temperature from 220 to 300 °C due to the improvement of crystal quality. [ABSTRACT FROM AUTHOR]

Neurogenesis in the adult mammalian hippocampus may contribute to repairing the brain after injury. The signals that regulate neurogenesis in the dentate gyrus following ischemic stroke insult are not well known. We have previously reported that inducible nitric oxide synthase (iNOS) expression is necessary for ischemia-stimulated neurogenesis in the adult dentate gyrus. Here, we show that mice subjected to 90 min of middle cerebral artery occlusion (MCAO) significantly increased the number of new neurons and up-regulated iNOS expression in the dentate gyrus. Blockade of the L-type voltage-gated Ca2+ channel (L-VGCC) prevented neurogenesis in the dentate gyrus and subventricular zone (SVZ), and down-regulated iNOS expression in the dentate gyrus after cerebral ischemia. This study suggests that Ca2+ influx through L-VGCC is involved in ischemia-induced neurogenesis by up-regulating iNOS expression. [ABSTRACT FROM AUTHOR]

Thin films of p-type ZnO:N have been obtained by thermally oxidizing zinc oxynitride films prepared by plasma enhanced chemical vapour deposition (PECVD). The p-type ZnO:N thin film with a hole concentration of 2.7 × 1016 cm-3 was obtained after an annealing process was conducted at 600 °C. A conductivity transition from n-type to p-type was observed, which was systematically researched via structural and compositional analyses. In terms of these analyses, it helped to better understand the properties and behaviour of nitrogen in ZnO. First, nitrogen was incorporated into ZnO films during the growth process to occupy oxygen positions, and also partly compensated some donors induced from non-stoichiometric (ZnO1–x) composition. Second, the amount of activated nitrogen gradually increased in an oxidizing atmosphere and exceeded those donor states to realize an effective compensation, yielding p-type conductivity during the course of thermal oxidation. [ABSTRACT FROM AUTHOR]

CA1 pyramidal neurons degenerate after transient forebrain ischemia, whereas neurons in other regions of the hippocampus remain intact. Here we show that in rat hippocampal CA1 neurons, forebrain ischemia induces the phosphorylation of the N-methyl-D-aspartate (NMDA) receptor 2A subunit at Ser1232 (phospho-Ser1232). Ser1232 phosphorylation is catalyzed by cyclin-dependent kinase 5 (Cdk5). Inhibiting endogenous Cdk5, or perturbing interactions between Cdk5 and NR2A subunits, abolished NR2A phosphorylation at Ser1232 and protected CA1 pyramidal neurons from ischemic insult. Thus, we conclude that modulation of NMDA receptors by Cdk5 is the primary intracellular event underlying the ischemic injury of CA1 pyramidal neurons. [ABSTRACT FROM AUTHOR]

Deals with a study which analyzed the molecular mechanisms contributing to long-term depression of the unitary gamma aminobutyric acid receptor-inhibitory synaptic currents. Materials and methods; Results; Discussion.

Presents a study which expressed enhanced green fluorescent protein in the adult rat hippocampus. Materials and methods; Results; Discussion.

We demonstrate the formation of n-type transparent SnO2 thin films by solution process. The influences of annealing temperature (200 °C–700 °C) on the microstructural, chemical, optical, and electrical performances of the SnO2 thin films are systematically investigated by a variety of characterization techniques. The results reveal that the solution-processed SnO2 thin film undergoes the elimination of organic and Cl-related residues along with the conversion of Sn(OH)4 to form crystalline SnO2, with the rising annealing temperature. This also leads to the improvement of the Hall mobility (from 0.3 to 13.7 cm2 V−1 s−1). Furthermore, the optimized SnO2 thin-film transistor annealed at 450 °C exhibits the highest saturation mobility of 0.511 cm2 V−1 s−1, on/off current ratio of 2.3  ×  104, on voltage of  −23.6 V, and subthreshold swing of 5.06. [ABSTRACT FROM AUTHOR]

White-light-emitting diode (LED) with effective energy conservation and long service life could be employed in numerous applications. In this study, the high-performance n-ZnO films were first prepared via pulsed laser deposition on p-GaN substrates and then the n-ZnO/p-GaN heterojunction LED was fabricated. This LED exhibits blue and yellow light emission, and their emission intensities can be tuned by adjustment of the fabrication parameters (e.g. oxygen pressure) and/or by introduction of a semi-insulating i-ZnO layer to form a p-GaN/i-ZnO/n-ZnO heterojunction. Thus, a facile approach has been proposed for the preparation of white LED. [ABSTRACT FROM AUTHOR]

We report the fabrication and characterization of high voltage AlGaN/GaN metal–oxide–semiconductor high-electron mobility transistors (MOSHEMTs) with selectively regrown In0.14Ga0.86N contact using a CMOS compatible gold-free process. Device with the regrown InGaN contact with a gate-to-drain spacing LGD of 5 µm achieves an off-state breakdown voltage VBR of 800 V and on-state resistance Ron of 2 mΩ·cm2. The VBR achieved in this work is higher than those of gold-free GaN MOSHEMTs with gate-to-drain spacing LGD below 10 µm. [ABSTRACT FROM AUTHOR]

An abstract of the article "EPAC Null Mutation Impairs Learning and Social Interactions Via Aberrant Regulation of miR-124 and Zif268 Translation," by Ying Yang, Xiaogana Shu, Dan Liu, Lei Pei, Lingqiang Zhu, Qing Tian, Jianzhi Wang and Youming Lu is presented.