Kamin blocking is disrupted by low-dose ketamine in mice: Further implications for aberrant stimulus processing in schizophrenia.

Previous studies have shown that low doses of ketamine, an N-methyl-D-aspartate receptor antagonist, produce aberrantly strong internal representations of associatively activated but absent stimuli in humans and nonhuman animals, suggesting the validity of ketamine treatment as a preclinical model of the positive symptoms of schizophrenia, including hallucinations and delusions. However, whether acute ketamine treatment also impairs the ability to ignore present but informationally redundant stimuli, which is another hallmark of schizophrenia, remains unclear. Accordingly, the present study investigated whether injections of low-dose ketamine attenuate Kamin blocking in an appetitive conditioning preparation in mice. Mice in the blocking group were initially trained with A+ conditioning (i.e., conditioned stimulus A paired with a sucrose solution), followed by compound AX+ training, before the conditioned responses to the cue X were tested in extinction. The animals in the control group received B+ training before the AX+ training. Half of the mice in each group received an injection of 16 mg/kg ketamine before each compound conditioning session and the extinction test, whereas the other half received saline. The results showed a reliable blocking effect in the saline-treated mice, whereas the blocking effect was absent in the ketamine-treated mice. Specifically, the absence of blocking was due to the ketamine-treated mice learning about the blocked cues. This finding further validates the use of low-dose ketamine as a preclinical model of schizophrenia. It also suggests a possible link between hallucination-like aberrant processing of absent events and a reduced ability to suppress attentional processing of task-irrelevant stimuli. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

CARD9-mediated macrophage responses and collagen fiber capsule formation caused by textured-type breast implants.

BACKGROUND: An increasing number of women are undergoing breast implantation for cosmetic purposes and for reconstructive purposes after breast excision. The surface morphology of the breast implant is one of the key factors associated with the induction of capsule contraction. The effect of surface morphology on the inflammatory response following implant insertion remains unclear, however. This study conducted comparative analyses to determine the effect of the textured and smooth surface morphology of silicone sheets. METHODS: Each type of silicone sheet was inserted into the subcutaneous pocket below the panniculus carnosus in C57BL/6 mice and mice with genetic disruption of CARD9, Dectin-1, Dectin-2, or Mincle. We also analyzed the collagen fiber capsule thickness, histological findings, and macrophage inflammatory response, including TGF-ß synthesis. RESULTS: We found that textured surface morphology contributed to the formation of collagen fiber capsules and the accumulation of fibroblasts and myofibroblasts, and was accompanied by the accumulation of TGF-ß-expressing macrophages and foreign-body giant cells. CARD9 deficiency attenuated collagen fiber capsule formation, macrophage responses, and TGF-ß synthesis, although the responsible C-type lectin receptors (CLRs) remain to be clarified. CONCLUSIONS: These results suggest that CARD9 may have a strong impact on silicone sheet insertion through the regulation of macrophage responses.

Cutaneous wound healing promoted by topical administration of heat-killed Lactobacillus plantarum KB131 and possible contribution of CARD9-mediated signaling.

Optimal conditions for wound healing require a smooth transition from the early stage of inflammation to proliferation, and during this time alternatively activated (M2) macrophages play a central role. Recently, heat-killed lactic acid bacteria (LAB), such as Lactobacillus plantarum (L. plantarum) have been reported as possible modulators affecting the immune responses in wound healing. However, how signaling molecules regulate this process after the administration of heat-killed LAB remains unclear. In this study, we examined the effect of heat-killed L. plantarum KB131 (KB131) administration on wound healing and the contribution of CARD9, which is an essential signaling adaptor molecule for NF-kB activation upon triggering through C-type lectin receptors, in the effects of this bacterium. We analyzed wound closure, histological findings, and inflammatory responses. We found that administration of KB131 accelerated wound closure, re-epithelialization, granulation area, CD31-positive vessels, and α-SMA-positive myofibroblast accumulated area, as well as the local infiltration of leukocytes. In particular, M2 macrophages were increased, in parallel with CCL5 synthesis. The acceleration of wound healing responses by KB131 was canceled in CARD9-knockout mice. These results indicate that the topical administration of KB131 accelerates wound healing, accompanying increased M2 macrophages, which suggests that CARD9 may be involved in these responses.

Synthesis and Characterization of the Orthorhombic Sn3 O4 Polymorph.

An unexplored tin oxide crystal phase (Sn3 O4 ) was experimentally synthesized via a facile hydrothermal method. After tuning the often-neglected parameters for the hydrothermal synthesis, namely the degree of filling of the precursor solution and the gas composition in the reactor head space, an unreported X-ray diffraction pattern was discovered. Through various characterization studies, such as Rietveld analysis, energy dispersive X-ray spectroscopy, and first-principles calculations, this novel material was characterized as orthorhombic mixed-valence tin oxide with the composition SnII 2 SnIV O4 . This orthorhombic tin oxide is a new polymorph of Sn3 O4 , which differs from the reported conventional monoclinic structure. Computational and experimental analyses showed that orthorhombic Sn3 O4 has a smaller band gap (2.0 eV), enabling greater absorption of visible light. This study is expected to improve the accuracy of hydrothermal synthesis and aid the discovery of new oxide materials.

Medical Doctors' Work-Life Balance and the Use of Household Chore Support Services.

Background: Achieving an optimal work-life balance (WLB) is an important social issue not only for workers in general but also for doctors due to the shortage of women doctors. The present study aims to survey doctors' WLB and their use of household chore support services (HCSS). Methods: A questionnaire survey was conducted with doctors working in Tottori Prefecture and a total of 289 responses (212 men, 77 women) were obtained and analyzed. To examine the relationship between gender and satisfaction with working patterns or with life for WLB, as well as the use of HCSS, a chi-squared test was conducted. Furthermore, a chi-squared test was conducted including age, marital status, whether or not they have preschool-aged children, and type of institution the participant worked. Results: A significant difference was found in type of institution the participant worked regarding satisfaction with work patterns and life. The proportion of those who have used HCSS was 12.5% of the total sample and was significantly higher for women than men (men: 8.5%; women: 23.4%). Regarding the reason to use HCSS, "to reduce the burden of household chores and childcare" and "to secure time for work" were most common with the same proportions, and amongst women, "to secure time for work" was the highest. Conclusion: Doctors working at a university hospital could have different work patterns and satisfaction with life compared to those working at other types of medical institutions. Additionally, the demand for HCSS was particularly high among women doctors, which suggests that HCSS may be used to reduce the burden of household chores and childcare, as well as to create time for work.

Machine learning-based analysis of overall stability constants of metal-ligand complexes.

The stability constants of metal(M)-ligand(L) complexes are industrially important because they affect the quality of the plating film and the efficiency of metal separation. Thus, it is desirable to develop an effective screening method for promising ligands. Although there have been several machine-learning approaches for predicting stability constants, most of them focus only on the first overall stability constant of M-L complexes, and the variety of cations is also limited to less than 20. In this study, two Gaussian process regression models are developed to predict the first overall stability constant and the n-th (n > 1) overall stability constants. Furthermore, the feature relevance is quantitatively evaluated via sensitivity analysis. As a result, the electronegativities of both metal and ligand are found to be the most important factor for predicting the first overall stability constant. Interestingly, the predicted value of the first overall stability constant shows the highest correlation with the n-th overall stability constant of the corresponding M-L pair. Finally, the number of features is optimized using validation data where the ligands are not included in the training data, which indicates high generalizability. This study provides valuable insights and may help accelerate molecular screening and design for various applications.

A behavioural correlate of the synaptic eligibility trace in the nucleus accumbens.

Reward reinforces the association between a preceding sensorimotor event and its outcome. Reinforcement learning (RL) theory and recent brain slice studies explain the delayed reward action such that synaptic activities triggered by sensorimotor events leave a synaptic eligibility trace for 1 s. The trace produces a sensitive period for reward-related dopamine to induce synaptic plasticity in the nucleus accumbens (NAc). However, the contribution of the synaptic eligibility trace to behaviour remains unclear. Here we examined a reward-sensitive period to brief pure tones with an accurate measurement of an effective timing of water reward in head-fixed Pavlovian conditioning, which depended on the plasticity-related signaling in the NAc. We found that the reward-sensitive period was within 1 s after the pure tone presentation and optogenetically-induced presynaptic activities at the NAc, showing that the short reward-sensitive period was in conformity with the synaptic eligibility trace in the NAc. These findings support the application of the synaptic eligibility trace to construct biologically plausible RL models.

Distinct Roles for Dectin-1 and Dectin-2 in Skin Wound Healing and Neutrophilic Inflammatory Responses.

C-type lectin receptors recognize microbial polysaccharides. The C-type lectin receptors such as dendritic cell-associated C-type lectin (Dectin)-1 and Dectin-2, which are triggered by ß-glucan and α-mannan, respectively, contribute to upregulation of the inflammatory response. Recently, we demonstrated that activation of the Dectin-2 signal delayed wound healing; in previous studies, triggering the Dectin-1 signal promoted this response. However, the precise roles of these C-type lectin receptors in skin wound healing remain unclear. This study was conducted to determine the roles of Dectin-1 and Dectin-2 in skin wound healing, with a particular focus on the kinetics of neutrophilic inflammatory response. Full-thickness wounds were created on the backs of C57BL/6 mice, and the effects of Dectin-1 or Dectin-2 deficiency and those of ß-glucan or α-mannan administration were examined. We also analyzed wound closure, histological findings, and neutrophilic inflammatory response, including neutrophil extracellular trap formation at the wound sites. We found that Dectin-1 contributed to the acceleration of wound healing by inducing early-phase neutrophil accumulation, whereas Dectin-2 was involved in prolonged neutrophilic responses and neutrophil extracellular trap formation, leading to delayed wound healing. Dectin-2 deficiency also improved collagen deposition and TGF-ß1 expression. These results suggest that Dectin-1 and Dectin-2 have different roles in wound healing through their different effects on the neutrophilic response.

Circular RNA circVAPA knockdown suppresses colorectal cancer cell growth process by regulating miR-125a/CREB5 axis.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor, and the overall prognosis of patients with advanced CRC is still unsatisfactory. Circular RNAs (circRNAs) vesicle-associated membrane protein-associated protein A (circVAPA) could act as an underlying biomarker in CRC. This study aimed to explore the mechanism of circVAPA in the regulation of CRC growth. METHODS: CircVAPA level was measured in CRC tumor tissues. The expression levels of circVAPA, VAPA mRNA, microRNA-125a (miR-125a), and cAMP response element binding 5 (CREB5) in CRC cells were detected by RT-qPCR. Cell cycle progression, migration and invasion, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by flow cytometry, transwell assays and Seahorse XF96 Glycolysis Analyzer, severally. The levels of glucose uptake, lactate and ATP production were examined by Glucose Uptake Colorimetric Assay kit, Lactate Assay kit and ATP Colorimetric Assay kit, respectively. The interaction between miR-125a and circVAPA or CREB5 was predicted by Starbase or DIANA TOOL, and verified by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. RESULTS: CircVAPA level was up-regulated in CRC tumor tissues. Expression levels of circVAPA and CREB5 were increased, and miR-125a was decreased in CRC cells. CircVAPA knockdown repressed CRC cells cycle progression, migration, invasion and glycolysis. CircVAPA acted as a miR-125a sponge to regulate CREB5 expression. Rescue assay confirmed that miR-125a deletion or CREB5 overexpression weakened the inhibitory effect of circVAPA knockdown on CRC growth. CONCLUSION: Our studies disclosed that circVAPA knockdown suppressed CRC cells cycle progression, migration, invasion and glycolysis partly by modulating miR-125a/CREB5 axis, suggesting a potential therapeutic strategy for CRC treatment.

Dopamine D2 receptors in discrimination learning and spine enlargement.

Dopamine D2 receptors (D2Rs) are densely expressed in the striatum and have been linked to neuropsychiatric disorders such as schizophrenia1,2. High-affinity binding of dopamine suggests that D2Rs detect transient reductions in dopamine concentration (the dopamine dip) during punishment learning3-5. However, the nature and cellular basis of D2R-dependent behaviour are unclear. Here we show that tone reward conditioning induces marked stimulus generalization in a manner that depends on dopamine D1 receptors (D1Rs) in the nucleus accumbens (NAc) of mice, and that discrimination learning refines the conditioning using a dopamine dip. In NAc slices, a narrow dopamine dip (as short as 0.4 s) was detected by D2Rs to disinhibit adenosine A2A receptor (A2AR)-mediated enlargement of dendritic spines in D2R-expressing spiny projection neurons (D2-SPNs). Plasticity-related signalling by Ca2+/calmodulin-dependent protein kinase II and A2ARs in the NAc was required for discrimination learning. By contrast, extinction learning did not involve dopamine dips or D2-SPNs. Treatment with methamphetamine, which dysregulates dopamine signalling, impaired discrimination learning and spine enlargement, and these impairments were reversed by a D2R antagonist. Our data show that D2Rs refine the generalized reward learning mediated by D1Rs.

Defect of Interferon γ Leads to Impaired Wound Healing through Prolonged Neutrophilic Inflammatory Response and Enhanced MMP-2 Activation.

Interferon (IFN)-γ is mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. Although IFN-γ is well known regarding its inhibitory effects on collagen synthesis by fibroblasts in vitro, information is limited regarding its role in wound healing in vivo. In the present study, we analyzed how the defect of IFN-γ affects wound healing. Full-thickness wounds were created on the backs of wild type (WT) C57BL/6 and IFN-γ-deficient (KO) mice. We analyzed the percent wound closure, wound breaking strength, accumulation of leukocytes, and expression levels of COL1A1, COL3A1, and matrix metalloproteinases (MMPs). IFN-γKO mice exhibited significant attenuation in wound closure on Day 10 and wound breaking strength on Day 14 after wound creation, characteristics that are associated with prolonged neutrophil accumulation. Expression levels of COL1A1 and COL3A1 mRNA were lower in IFN-γKO than in WT mice, whereas expression levels of MMP-2 (gelatinase) mRNA were significantly greater in IFN-γKO than in WT mice. Moreover, under neutropenic conditions created with anti-Gr-1 monoclonal antibodies, wound closure in IFN-γKO mice was recovered through low MMP-2 expression levels. These results suggest that IFN-γ may be involved in the proliferation and maturation stages of wound healing through the regulation of neutrophilic inflammatory responses.

A rare case of peritoneal deposits with carbon pigmentation after preoperative endoscopic tattooing for sigmoid colon cancer.

PURPOSE: We report a case in which pigmented peritoneal deposits were found during laparoscopic surgery following preoperative endoscopic tattooing for sigmoid colon cancer. METHODS: The patient's clinical, endoscopic, and histological data from the Niigata City General Hospital were reviewed, as well as the literature on laparoscopic surgery involving the preoperative endoscopic tattoo, with a focus on the relevance of peritoneal deposits and tattooing ink. RESULTS: A 71-year-old man presented to our hospital complaining of vomiting and abdominal distention. Abdominal computed tomography revealed obstructive sigmoid colon cancer. An emergency endoscopic colon stenting procedure and injection of 0.2 ml India ink to the submucosal layer of the tumor's anal side were performed. Laparoscopic-assisted sigmoid colectomy was done 14 days after stenting. At surgery, seven small peritoneal deposits were seen in the rectovesical pouch and at the site adjacent to the tumor. All peritoneal deposits were stained by the ink. Gross leakage of the ink into extraintestinal sites was seen. The seven peritoneal deposits were resected under laparoscope. Histological findings revealed that the seven peritoneal deposits were composed of adenocarcinoma and carbon pigments. Immunohistochemical staining for cluster of differentiation 163 showed that the carbon pigments in the peritoneal deposits were within macrophages. CONCLUSIONS: The possibility of the tattooing procedure causing peritoneal dissemination cannot be completely denied, but it can be hypothesized that the carbon pigmentation was transferred to peritoneal deposits by macrophages. In the future, we hope that this phenomenon becomes a keystone for diagnoses and treatments for peritoneal dissemination.

Dectin-2-Mediated Signaling Leads to Delayed Skin Wound Healing through Enhanced Neutrophilic Inflammatory Response and Neutrophil Extracellular Trap Formation.

Dendritic cell-associated C-type lectin-2 (i.e., dectin-2) recognizes fungal polysaccharides, including α-mannan. Dectin-2-mediated recognition of fungi, such as Candida albicans, leads to NF-κB activation, which induces production of inflammatory cytokines. However, the role of dectin-2 in skin wound healing remains unclear. In this study, we sought to determine how dectin-2 deficiency and the administration of α-mannan affected the wound healing process. Full-thickness wounds were created on the backs of wild type C57BL/6 and dectin-2-deficient mice. We analyzed wound closure, histological findings, and re-epithelialization. We also examined the neutrophilic inflammatory responses and neutrophil extracellular trap (NET)-osis at the wound sites after administration of α-mannan. The percent wound closure and re-epithelialization was significantly accelerated in dectin-2-knockout mice compared with wild-type mice on days 3 and 5 after wounding. In contrast, administration of α-mannan delayed wound closure in wild-type mice, and these responses were canceled in dectin-2-knockout mice. Furthermore, mice administered α-mannan, neutrophil infiltration was prolonged, and the expression of citrullinated histone, an indicator of NETosis, at the wound sites was accelerated. Administration of a neutrophil elastase inhibitor significantly improved the delayed wound healing caused by α-mannan. These results suggest that dectin-2 may have a deep impact on the skin wound healing process through regulation of neutrophilic responses.

Comparison of perioperative and oncological outcome of thoracoscopic esophagectomy in left decubitus position and in prone position for esophageal cancer.

PURPOSE: The aim of this study was to clarify the differences between thoracoscopic esophagectomy in the left decubitus position (LP) and in the prone position (PP) in terms of short-term perioperative outcomes and long-term oncological outcomes after more than 5 years of follow-up. METHODS: Patients with esophageal cancer who underwent thoracoscopic esophagectomy and were followed up for more than 5 years were analyzed retrospectively. Of 142 patients, 72 underwent LP esophagectomy and 70 underwent PP esophagectomy. Operation time, blood loss, operative morbidity, mortality, length of hospital stay, and the number of dissected lymph nodes were compared to evaluate short-term outcomes. Cancer recurrence and overall survival were compared to examine long-term outcomes. RESULTS: Patient and tumor characteristics were not different between the LP and PP groups except for the rate of neoadjuvant chemotherapy. Blood loss was significantly lower in the PP group than in the LP group. Incidence of Clavien-Dindo (C.D.) grade ≥ III complications was significantly lower in the PP group than in the LP group. Pulmonary complications were also significantly lower in the PP group than in the LP group. Operation type (LP versus PP) was identified as an independent risk factor for pulmonary complications (odds ratio 0.27, p = 0.03) by multivariate analysis. Cancer recurrence rate, initial recurrence site, and overall survival rate were not different between the two groups. CONCLUSIONS: PP is regarded as a less invasive procedure than LP with the same oncological effect.

Rhinoplasty of a severe broad nose deformity caused by radical surgery on the maxillary sinus in childhood.

We are the first to report a case of severe broad nose deformity caused by radical surgery on the maxillary sinus in childhood. We treated this broad nose deformity with closed rhinoplasty.

Inactivation of Cerebellar Cortical Crus II Disrupts Temporal Processing of Absolute Timing but not Relative Timing in Voluntary Movements.

Several recent studies have demonstrated that the cerebellum plays an important role in temporal processing at the scale of milliseconds. However, it is not clear whether intrinsic cerebellar function involves the temporal processing of discrete or continuous events. Temporal processing during discrete events functions by counting absolute time like a stopwatch, while during continuous events it measures events at intervals. During the temporal processing of continuous events, animals might respond to rhythmic timing of sequential responses rather than to the absolute durations of intervals. Here, we tested the contribution of the cerebellar cortex to temporal processing of absolute and relative timings in voluntary movements. We injected muscimol and baclofen to a part of the cerebellar cortex of rats. We then tested the accuracy of their absolute or relative timing prediction using two timing tasks requiring almost identical reaching movements. Inactivation of the cerebellar cortex disrupted accurate temporal prediction in the absolute timing task. The rats formed two groups based on the changes to their timing accuracy following one of two distinct patterns which can be described as longer or shorter declines in the accuracy of learned intervals. However, a part of the cerebellar cortical inactivation did not affect the rats' performance of relative timing tasks. We concluded that a part of the cerebellar cortex, Crus II, contributes to the accurate temporal prediction of absolute timing and that the entire cerebellar cortex may be unnecessary in cases in which accurately knowing the absolute duration of an interval is not required for temporal prediction.

Spike-coding mechanisms of cerebellar temporal processing in classical conditioning and voluntary movements.

Time is a fundamental and critical factor in daily life. Millisecond timing, which is the underlying temporal processing for speaking, dancing, and other activities, is reported to rely on the cerebellum. In this review, we discuss the cerebellar spike-coding mechanisms for temporal processing. Although the contribution of the cerebellum to both classical conditioning and voluntary movements is well known, the difference of the mechanisms for temporal processing between classical conditioning and voluntary movements is not clear. Therefore, we review the evidence of cerebellar temporal processing in studies of classical conditioning and voluntary movements and report the similarities and differences between them. From some studies, which used tasks that can change some of the temporal properties (e.g., the duration of interstimulus intervals) with keeping identical movements, we concluded that classical conditioning and voluntary movements may share a common spike-coding mechanism because simple spikes in Purkinje cells decrease at predicted times for responses regardless of the intervals between responses or stimulation.

Serum aluminum levels in dialysis patients after sclerotherapy of internal hemorrhoids with aluminum potassium sulfate and tannic acid.

PURPOSE: Aluminum potassium sulfate and tannic acid (ALTA) is an effective sclerosing agent for internal hemorrhoids. However, it is contraindicated for patients with chronic renal failure on dialysis, because the aluminum in ALTA can cause aluminum encephalopathy when it is not excreted effectively. We conducted this study to measure the serum aluminum concentrations and observe for symptoms relating to aluminum encephalopathy in dialysis patients after ALTA therapy. METHODS: Ten dialysis patients underwent ALTA therapy for hemorrhoids. We measured their serum aluminum concentrations and observed them for possible symptoms of aluminum encephalopathy. RESULTS: The total injection volume of ALTA solution was 31 mL (24-37). The median serum aluminum concentration before ALTA therapy was 9 µg/L, which increased to 741, 377, and 103 µg/L, respectively, 1 h, 1 day, and 1 week after ALTA therapy. These levels decreased rapidly, to 33 µg/L by 1 month and 11 µg/L by 3 months after ALTA therapy. No patient suffered symptoms related to aluminum encephalopathy. CONCLUSIONS: Although the aluminum concentrations increased temporarily after ALTA therapy, dialysis patients with levels below 150 µg/L by 1 week and thereafter are considered to be at low risk of the development of aluminum encephalopathy.

Experimental assessment of a novel intramedullary nail for callus distraction by the segmental bone transport method.

BACKGROUND: Segmental bone transport (SBT) is a revolutionary method for treating extensive bone defects, and it is in wide clinical use. Although external fixation is generally used to perform SBT, it is associated with problems such as complications due to pin placement and limitations of the amount and rate of lengthening. As a way to overcome these problems we developed a novel intramedullary (IM) nail for SBT that minimizes damage to the surrounding tissue and improves the amount and rate of bone lengthening. The purpose of this study was to perform SBT in the femur of beagle dogs using the novel IM nail that we devised, and to evaluate the morphology and quality of the regenerated bone and circulation status in the surrounding tissue. We also considered the possibilities and limitations of the IM in regard to clinical application. METHODS: This experiment was conducted on six beagle dogs. The novel IM nail we devised was inserted into the marrow cavity of the femur, and a 30-mm bone defect was created. After a 7-day postoperative waiting period, a bone segment was transported by 1.0 mm per day in two 0.5-mm increments. Because the nail broke in two dogs, they received only partial elongation by 15 mm over a 15-day period, with a 15-mm defect remaining, whereas full elongation by 30 mm in 30 days was performed in the other four dogs. The elongation was followed by a 30-day bone hardening period. RESULTS: The macroscopic and histological results demonstrated that high-quality, new bone had replaced the 30-mm bone defect created in the femur of all six dogs. The density and number of blood vessels that had penetrated the elongated segment of bone from the surrounding muscles was greater than in the corresponding segment of the contralateral femur, which served as a control. The results imply that the traction stimulus induced vigorous angiogenesis in the surrounding tissue. CONCLUSION: We concluded that this method has tremendous potential for clinical application, and will overcome the limitations of conventional external fixators.

Novel behavioral tasks to explore cerebellar temporal processing in milliseconds in rats.

Temporal processing in milliseconds has been reported to rely on the cerebellum; however, no detailed neuronal mechanisms have been published yet. This is because there are too few studies on the relationship between temporal processing in milliseconds and cerebellar neuronal spikes that organize behavioral timing. To demonstrate this relationship, it is necessary to record the spike activity while the animal is performing a behavioral task that requires specific temporal processing in milliseconds. In this study, we describe two novel timing tasks. These behavioral tasks comprise the following schedules: fixed ratio (FR) and differential reinforcement of low rate (DRL). This paper describes the behavioral differences between the absolute timing of individual intervals (duration based timing) and the relative timing of rhythmic sequences (beat-based timing) in these novel tasks.