Long-lasting forms of plasticity through patterned ultrasound-induced brainwave entrainment.

Achieving long-lasting neuronal modulation with low-intensity, low-frequency ultrasound is challenging. Here, we devised theta burst ultrasound stimulation (TBUS) with gamma bursts for brain entrainment and modulation of neuronal plasticity in the mouse motor cortex. We demonstrate that two types of TBUS, intermittent and continuous TBUS, induce bidirectional long-term potentiation or depression-like plasticity, respectively, as evidenced by changes in motor-evoked potentials. These effects depended on molecular pathways associated with long-term plasticity, including N-methyl-d-aspartate receptor and brain-derived neurotrophic factor/tropomyosin receptor kinase B activation, as well as de novo protein synthesis. Notably, bestrophin-1 and transient receptor potential ankyrin 1 play important roles in these enduring effects. Moreover, pretraining TBUS enhances the acquisition of previously unidentified motor skills. Our study unveils a promising protocol for ultrasound neuromodulation, enabling noninvasive and sustained modulation of brain function.

Automating licking bias correction in a two-choice delayed match-to-sample task to accelerate learning.

Animals often display choice bias, or a preference for one option over the others, which can significantly impede learning new tasks. Delayed match-to-sample (DMS) tasks with two-alternative choices of lickports on the left and right have been widely used to study sensory processing, working memory, and associative memory in head-fixed animals. However, extensive training time, primarily due to the animals' biased licking responses, limits their practical utility. Here, we present the implementation of an automated side bias correction system in an olfactory DMS task, where the lickport positions and the ratio of left- and right-rewarded trials are dynamically adjusted to counterbalance mouse's biased licking responses during training. The correction algorithm moves the preferred lickport farther away from the mouse's mouth and the non-preferred lickport closer, while also increasing the proportion of non-preferred side trials when biased licking occurs. We found that adjusting lickport distances and the proportions of left- versus right-rewarded trials effectively reduces the mouse's side bias. Further analyses reveal that these adjustments also correlate with subsequent improvements in behavioral performance. Our findings suggest that the automated side bias correction system is a valuable tool for enhancing the applicability of behavioral tasks involving two-alternative lickport choices.

Reward learning improves social signal processing in autism model mice.

Social and reward signal processing and their association are critical elements of social motivation. Despite the use of reward learning to improve the social interactions of patients with autism spectrum disorder (ASD), the underlying neural mechanisms are unknown. Here, we found different yet conjunct neuronal representations of social and reward signals in the mouse medial prefrontal cortex (mPFC). We also found that social signal processing is selectively disrupted, whereas reward signal processing is intact in the mPFC of Shank2-knockout mice, a mouse model of ASD. Furthermore, reward learning not only allows Shank2-knockout mice to associate social stimuli with reward availability, but it also rescues the impaired social signal processing. These findings provide insights into the neural basis for the therapeutic use of reward learning in ASD.

A quantitative analysis of spontaneous alternation behaviors on a Y-maze reveals adverse effects of acute social isolation on spatial working memory.

Animals tend to alternate between different choices, which requires the ability to remember recent choices. The Y-maze spontaneous alternation test is widely used in various animal models for assessing short-term memory, and its precise evaluation depends upon the accurate determination of the arm visit sequence. However, an objective method for defining arm visits is lacking owing to uncertainty regarding the extent to which an animal must go into the arm to be considered visited. Here, we conducted quantitative analyses on mice behavior in the Y-maze while systematically varying the arm visit threshold and assessed the effect of acute social isolation on spatial working memory. Our results revealed that 24-h social isolation significantly reduced spontaneous alternation rate when the arm threshold was set at the distal part of the arm. Furthermore, the memory of the recently visited arms faded away faster in the socially isolated mice. However, other behavioral factors were comparable to those of the group-housed mice, indicating a specific impairment of short-term memory. Our findings suggest that the location of arm visit threshold is critical for the precise evaluation of short-term memory, and our study provides a method for comprehensively and systematically assessing spontaneous alternation behavior in the Y-maze.

Discordant renal progression of Fabry disease in male monozygotic twins: a case report.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A (α-GAL). Clinical phenotypes tend to vary in monozygotic female twins because mutations are located on the X-chromosome, whereas similar phenotypes are found in male monozygotic twins. Here we report the case of male monozygotic twins with FD presenting with distinguishable renal phenotypes. Case: A 49-year-old male patient who visited the hospital with proteinuria 14 years prior was readmitted for the same issue. His monozygotic twin brother had started hemodialysis 6 months prior due to renal failure of unknown origin. The patient's renal function was within the normal range, while his spot urine protein-to-creatinine ratio was 557 mg/g. Echocardiography revealed left ventricular hypertrophy (LVH). The findings of a renal biopsy were consistent with FD. Genetic testing identified a c.656T>C mutation in the GLA gene, and α-GAL activity was significantly decreased. Genetic screening of his family clarified that his mother, older sister, twin brother, and his daughter had the same genetic mutations. The patient received enzyme replacement therapy 34 times. Subsequently, migalastat was initiated that continues today. Renal function and proteinuria remain stable, and the LVH has mildly improved. Conclusion: This is the first case of male monozygotic twins expressing different progressions of FD. Our findings demonstrate the possibility that environmental or epigenetic factors may critically influence genotype-phenotype discordance.

Dynamic and stable hippocampal representations of social identity and reward expectation support associative social memory in male mice.

Recognizing an individual and retrieving and updating the value information assigned to the individual are fundamental abilities for establishing social relationships. To understand the neural mechanisms underlying the association between social identity and reward value, we developed Go-NoGo social discrimination paradigms that required male subject mice to distinguish between familiar mice based on their individually unique characteristics and associate them with reward availability. We found that mice could discriminate individual conspecifics through a brief nose-to-nose investigation, and this ability depended on the dorsal hippocampus. Two-photon calcium imaging revealed that dorsal CA1 hippocampal neurons represented reward expectation during social, but not non-social tasks, and these activities were maintained over days regardless of the identity of the associated mouse. Furthermore, a dynamically changing subset of hippocampal CA1 neurons discriminated between individual mice with high accuracy. Our findings suggest that the neuronal activities in CA1 provide possible neural substrates for associative social memory.

New Scanning Strategy for More Accurate Implant Scanbody Alignment: Short Communication.

This manuscript presents a more accurate methodology, in comparison to extant approaches, that enables errorless congruence between an implant scanbody and its counterparts in the scanbody library of a dental computer-aided design (CAD) application. The proposed method deletes corners and difficult intraoral scanning regions and selects only the remaining flat and wide scanbody planes in the library. Achieving overlap between the portions of the actual scanbody data without distortion using an intraoral scanner is a novel development that is expected to represent a new standard in scanbody library alignment.

Complete plastid genome of Cumathamnion serrulatum (Ceramiales, Rhodophyta).

We report the complete plastid genome of Cumathamnion serrulatum, also known as Delesseria serrulata. The plastid genome was 174,192 bp in size. Annotation showed there were 193 protein coding genes, three ribosomal RNAs, and 29 transfer RNAs. One intron was found, and the GC content was 27.2%. The maximum likelihood tree with the concatenated 177 plastid coding genes showed a strong monophyletic relationship to Membranoptera spp. within the Ceramiales.

Superimposition of a cone beam computed tomography (CBCT) scan and a photograph: A dental technique.

Various methods of combining facial and intraoral information have been described. However, overlapping errors lead to errors. This article describes a 3D face model that uses a UV mapping technique. The combination of soft-tissue information extracted from cone beam computed tomography (CBCT) and a straightforward facial photograph provides more accurate data than with conventional methods.

Aortic Remodeling and Clinical Outcomes in Type B Aortic Dissection According to the Timing of Thoracic Endovascular Aortic Repair.

BACKGROUND: The objective of the study was to investigate aortic remodeling and clinical outcomes after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (AD) according to timing of the procedure. METHODS: A total of 87 patients with type B AD who underwent TEVAR at 2 centers were included in this retrospective analysis. Patients were divided into acute/subacute (≤6 weeks, n = 35), early chronic (6 weeks to 1 year, n = 20), and late chronic (>1 year, n = 32) groups according to the timing of TEVAR after symptom onset. Changes in aorta dimensions on serial computed tomography angiograms and clinical outcomes were evaluated. RESULTS: AD complications were the most common indication for TEVAR in the acute/subacute group, whereas aortic expansion was the main reason in the early and late chronic groups. Maximum total aorta diameter (46.6 ± 10.6 vs. 54.8 ± 9.8 vs. 56.7 ± 10.1 mm, P < 0.001) and false lumen diameter (30.9 ± 11.0 vs. 35.2 ± 12.0 vs. 39.9 ± 13.4 mm, P = 0.013) were smaller in the acute/subacute group than in the early and late chronic groups. At 1-year follow-up, maximum total aorta diameter was decreased in the acute/subacute and early chronic groups and increased in the late chronic group (-4.3 ± 9.3 vs. -5.2 ± 6.9 vs. 2.5 ± 4.6 mm, P < 0.001). Survival free from the major adverse aortic event (death, aortic rupture, or reintervention) at 5 years after TEVAR was lowest in the late chronic group (92.6% vs. 88.2% vs. 73.1%, P = 0.033) but not significantly different between the acute/subacute and early chronic groups (P = 0.680). CONCLUSIONS: TEVAR in the acute/subacute and early chronic phases of type B AD resulted in similar aortic remodeling and clinical outcomes, which were more favorable than those with TEVAR performed during late chronic AD. This finding suggests 1 year after the onset of type B AD symptoms as the upper time threshold for TEVAR to achieve optimal aortic remodeling and safety.

Evaluation of Bioabsorbable Mg-Mn Alloy with Anodic Oxidation Treatment.

Magnesium alloys as biodegradable materials have been examined that may replace bone screws and plates in recent studies. But the velocity control of magnesium alloy is very difficult. Until now, the magnesium alloys degrade very fast, thus it couldn't maintain the function in clinical field. Thus the purpose of this study is to evaluate the degradability of anodized magnesium alloy for control the velocity. For this experiment, a Mg-xMn (x = 0, 0.5, 1 wt%) binary alloy was cast in argon gas (99.99%) atmosphere. The specimens of the surface treatment group were anodized for 15 minutes at a voltage of 120 V at room temperature using calcium gluconate, sodium hexametaphosphate, and sodium hydroxide electrolyte. For the mechanical test, SEM, roughness test, hardness test were examined. The degradation test was conducted to measure the hydrogen gas formation volume. For biologic test, cell viability were tested. After anodic oxidation treatment, the surface showed the crater formation, the size of craters were about 200~300 nm. Among nonanodized group, the Mg-0.5Mn showed the highest Vickers hardness and cell viability. However for biodegradability test, Mg-1Mn showed the lowest the hydrogen gas formation. For anodic oxidation treatment, anodic oxidation treatment makes rougher surface, higher hardness, good cell response and lower degradation rate. Overall, anodized Mg-1Mn showed the possibility for clinical application in bone screw and bone plate.

A Hybrid Dental Model Concept Utilizing Fused Deposition Modeling and Digital Light Processing 3D Printing.

Currently, 3D printers, especially digital light processing (DLP) printers, are widely used in clinical dentistry. However, due to the shrinkage property of resin, their accuracy is not optimal for full-arch dental model printing. To overcome these limitations, fused deposition modeling (FDM) with filament that undergoes minimum shrinkage was introduced. Accordingly, a combination of FDM printing with the specific tooth die output of DLP printing for the full-arch dental model is proposed in the present report.

Transient effect of mossy fiber stimulation on spatial firing of CA3 neurons in familiar and novel environments.

Hippocampal mossy fibers have long been proposed to impose new patterns to learn onto CA3 neurons during new memory formation. However, inconsistent with this theory, we found in our previous study that mossy fiber stimulation induces only transient changes in CA3 spatial firing in a familiar environment. Here, we tested whether mossy fiber stimulation affects CA3 spatial firing differently between familiar and novel environments. We compared spatial firing of CA3 neurons before and after optogenetic stimulation of mossy fibers in freely behaving mice in a familiar and three sets of novel environments. We found that CA3 neurons are more responsive to mossy fiber stimulation in the novel than familiar environments. However, we failed to obtain evidence for long-lasting effect of mossy fiber stimulation on spatial firing of CA3 neurons in both the familiar and novel environments. Our results provide further evidence against the view that mossy fibers carry teaching signals.

Modified digital workflow for artificial tooth exchange in a complete denture: A dental technique.

Duplication of complete dentures by using digital technology is now widely practiced. However, the method of accepting only the cameo surface of dentures and forming a new artificial tooth arrangement by using analog techniques is still complex and time-consuming. A method for creating a new denture by implementing various artificial tooth arrangements by using a computer-aided design (CAD) software program after importing the existing denture cameo surface as is into the software is introduced. The technique helps solve patient discomfort due to occlusal problems in patients with complete dentures.

Denture flask fabrication using fused deposition modeling three-dimensional printing.

PURPOSE: This paper describes a method for making a customized denture flask using fused deposition modeling (FDM) by three-dimensional (3D) printing. We have proposed a new digital dental prosthesis using conventional dental base materials and artificial teeth. METHODS: Using the universal development system software, a denture-designed Standard Tessellation Language (STL) file and a denture flask STL file were superimposed, and the denture region was set as an empty space. After setting the offset value to 200µm between the denture base and teeth for artificial tooth positioning, the flask was created by FDM 3D printing. Conventional artificial teeth were inserted into the 3D-printed flask, and resin packing, finishing, and polishing were performed using the conventional method for fabricating the complete denture. CONCLUSIONS: The 3D printing materials used to make digital dental prostheses have not yet been fully validated. Therefore, the production of a 3D-printed denture flask, which can use conventional complete denture materials, presents a new alternative to the digital fabrication of dentures.

Transient effect of mossy fiber stimulation on spatial firing of CA3 neurons.

Strong hippocampal mossy fiber synapses are thought to function as detonators, imposing "teaching" signals onto CA3 neurons during new memory formation. For an empirical test of this long-standing view, we examined effects of optogenetically stimulating mossy fibers on spatial firing of CA3 neurons in freely-moving mice. We found that spatially restricted mossy fiber stimulation drives novel place-specific firing in some CA3 pyramidal neurons. Such neurons comprise only a minority, however, and many more CA3 neurons showed inhibited spatial firing during mossy fiber stimulation. Also, changes in spatial firing induced by mossy fiber stimulation, both activated and inhibited, reverted immediately upon stimulation termination, leaving CA3 place fields unaltered. Our results do not support the traditional view that mossy fibers impose teaching signals onto CA3 network, and show robustness of established CA3 spatial representations.

In Vivo Patch-Clamp Recording in Awake Head-Fixed Rodents.

Whole-cell recording has been used to measure and manipulate a neuron's spiking and subthreshold membrane potential, allowing assessment of the cell's inputs and outputs as well as its intrinsic membrane properties. This technique has also been combined with pharmacology and optogenetics as well as morphological reconstruction to address critical questions concerning neuronal integration, plasticity, and connectivity. This protocol describes a technique for obtaining whole-cell recordings in awake head-fixed animals, allowing such questions to be investigated within the context of an intact network and natural behavioral states. First, animals are habituated to sit quietly with their heads fixed in place. Then, a whole-cell recording is obtained using an efficient, blind patching protocol. We have successfully applied this technique to rats and mice.

Efficient Method for Whole-Cell Recording in Freely Moving Rodents Using Ultraviolet-Cured Collar-Based Pipette Stabilization.

Whole-cell recording is a key technique for investigating synaptic and cellular mechanisms underlying various brain functions. However, because of its high sensitivity to mechanical disturbances, applying the whole-cell recording method to freely moving animals has been challenging. Here, we describe a technique for obtaining such recordings in freely moving, drug-free animals with a high success rate. This technique involves three major steps: obtaining a whole-cell recording from awake head-fixed animals, reliable and efficient stabilization of the pipette with respect to the animal's head using an ultraviolet (UV)-transparent collar and UV-cured adhesive, and rapid release of the animal from head fixation without loss of the recording. This technique has been successfully applied to obtain intracellular recordings from the hippocampus of freely moving rats and mice exploring a spatial environment, and should be generally applicable to other brain areas in animals engaged in a variety of natural behaviors.

Whole-Cell Recording in the Awake Brain.

Intracellular recording is an essential technique for investigating cellular mechanisms underlying complex brain functions. Despite the high sensitivity of the technique to mechanical disturbances, intracellular recording has been applied to awake, behaving, and even freely moving, animals. Here we summarize recent advances in these methods and their application to the measurement and manipulation of membrane potential dynamics for understanding neuronal computations in behaving animals.

Costimulation of AMPA and metabotropic glutamate receptors underlies phospholipase C activation by glutamate in hippocampus.

Glutamate, a major neurotransmitter in the brain, activates ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs, respectively). The two types of glutamate receptors interact with each other, as exemplified by the modulation of iGluRs by mGluRs. However, the other way of interaction (i.e., modulation of mGluRs by iGluRs) has not received much attention. In this study, we found that group I mGluR-specific agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) alone is not sufficient to activate phospholipase C (PLC) in rat hippocampus, while glutamate robustly activates PLC. These results suggested that additional mechanisms provided by iGluRs are involved in group I mGluR-mediated PLC activation. A series of experiments demonstrated that glutamate-induced PLC activation is mediated by mGluR5 and is facilitated by local Ca(2+) signals that are induced by AMPA-mediated depolarization and L-type Ca(2+) channel activation. Finally, we found that PLC and L-type Ca(2+) channels are involved in hippocampal mGluR-dependent long-term depression (mGluR-LTD) induced by paired-pulse low-frequency stimulation, but not in DHPG-induced chemical LTD. Together, we propose that AMPA receptors initiate Ca(2+) influx via the L-type Ca(2+) channels that facilitate mGluR5-PLC signaling cascades, which underlie mGluR-LTD in rat hippocampus.