Kinetics formulation for Two-Dimensional Growth Behavior of Water/Ice Interface on Si Substrate.

Sublimation drying is used in the drying process of semiconductor device manufacturing. However, the solidification behavior mechanics of sublimation agents on substrates has not been clarified. Therefore, the properties of solidified films within substrate surfaces can become nonuniform, leading to their collapse. This study aimed to analyze the interface growth behavior during the cooling and solidification of a water/ice system as a basic case and to clarify the dynamic mechanism of the solidification behavior of liquid films on Si substrates. The solidification behavior of a water/ice system on Si substrates was captured on a video at different cooling rates. The recorded video was subjected to a digital image analysis to examine the crystal morphology and quantify the interface growth rate. The least-squares method with kinetic formulas was used to evaluate the feasibility of fitting the temperature variation to the interface growth rate. A visual examination of the morphology of interfacial growth revealed that it can be classified into four morphologies. The proposed kinetic equation describes the experimental results regarding the temperature dependence of the interfacial growth rate. Through image analysis, the interface growth rate of water and ice was quantified, and an evaluation formula was proposed.

Cerebellar Contributions to the Basal Ganglia Influence Motor Coordination, Reward Processing, and Movement Vigor.

Both the cerebellum and the basal ganglia are known for their roles in motor control and motivated behavior. These two systems have been classically considered as independent structures that coordinate their contributions to behavior via separate cortico-thalamic loops. However, recent evidence demonstrates the presence of a rich set of direct connections between these two regions. Although there is strong evidence for connections in both directions, for brevity we limit our discussion to the better-characterized connections from the cerebellum to the basal ganglia. We review two sets of such connections: disynaptic projections through the thalamus and direct monosynaptic projections to the midbrain dopaminergic nuclei, the VTA and the SNc. In each case, we review the evidence for these pathways from anatomic tracing and physiological recordings, and discuss their potential functional roles. We present evidence that the disynaptic pathway through the thalamus is involved in motor coordination, and that its dysfunction contributes to motor deficits, such as dystonia. We then discuss how cerebellar projections to the VTA and SNc influence dopamine release in the respective targets of these nuclei: the NAc and the dorsal striatum. We argue that the cerebellar projections to the VTA may play a role in reward-based learning and therefore contribute to addictive behavior, whereas the projection to the SNc may contribute to movement vigor. Finally, we speculate how these projections may explain many of the observations that indicate a role for the cerebellum in mental disorders, such as schizophrenia.

The obesity paradox in Japanese COVID-19 patients.

Purpose: To investigate the effect of obesity on mortality and invasive respiratory care (IRC) in patients with COVID-19. Methods: We studied 1,105 patients for 34 months and collected data. The primary outcome was all-cause death at 29 days. The secondary outcome was IRC indicated by a pulse oximetry rate below 93% at a mask oxygenation rate of 5 L/min or more. Results: Age- and sex-adjusted multivariate regression analysis for 29-day deaths showed the significance of body mass index (BMI) > 19.6 kg/m2 (odds ratio 0.117, 95% confidence interval 0.052-0.265, P<0.001). The graphs with BMI in the abscissa showed, within a BMI between 11 and 25 kg/m2, a decreasing pattern for mortality and IRC rate, and no increase in overweight. Conclusion: In Japanese COVID-19 patients, the risk of mortality and the IRC rate decreased in underweight patients and remained low in overweight patients, suggesting the importance of the obesity paradox.

CXCL12 promotes CCR7 ligand-mediated breast cancer cell invasion and migration toward lymphatic vessels.

Chemokines are a family of cytokines that mediate leukocyte trafficking and are involved in tumor cell migration, growth, and progression. Although there is emerging evidence that multiple chemokines are expressed in tumor tissues and that each chemokine induces receptor-mediated signaling, their collaboration to regulate tumor invasion and lymph node metastasis has not been fully elucidated. In this study, we examined the effect of CXCL12 on the CCR7-dependent signaling in MDA-MB-231 human breast cancer cells to determine the role of CXCL12 and CCR7 ligand chemokines in breast cancer metastasis to lymph nodes. CXCL12 enhanced the CCR7-dependent in vitro chemotaxis and cell invasion into collagen gels at suboptimal concentrations of CCL21. CXCL12 promoted CCR7 homodimer formation, ligand binding, CCR7 accumulation into membrane ruffles, and cell response at lower concentrations of CCL19. Immunohistochemistry of MDA-MB-231-derived xenograft tumors revealed that CXCL12 is primarily located in the pericellular matrix surrounding tumor cells, whereas the CCR7 ligand, CCL21, mainly associates with LYVE-1+ intratumoral and peritumoral lymphatic vessels. In the three-dimensional tumor invasion model with lymph networks, CXCL12 stimulation facilitates breast cancer cell migration to CCL21-reconstituted lymphatic networks. These results indicate that CXCL12/CXCR4 signaling promotes breast cancer cell migration and invasion toward CCR7 ligand-expressing intratumoral lymphatic vessels and supports CCR7 signaling associated with lymph node metastasis.

Sotrovimab use in Japanese inpatients with COVID-19: post-infusion adverse events.

BACKGROUND: Sotrovimab neutralizing SARS-CoV-2 remained effective at the advent of B.1 lineage of the Omicron variant in outpatients. Primarily for hospitalized patients, however, the Japanese government regulated to administer this antibody agent. As this regulation enabled close monitoring in inpatients to investigate post-infusion adverse events (AEs) and efficacy, we attempted a retrospective study while the Omicron BA.1 lineage was dominant regionally. METHODS: Subjects were inpatients with COVID-19 who received infusion of sotrovimab in our institute. In line with previous clinical trials, we included patients at risk of COVID-19 worsening and SARS-CoV-2 vaccinees, who were hospitalized as directed by the government. For statistical analyses, we reviewed background factors of demographics, imaging, and laboratory findings for the outcome infusion-related reactions including post-infusion pyrexia over 38 degrees Celsius and/or pulse oximetry below 94%. RESULTS: In a total of 139 patients, the follow-up period had a median of 200 days (range, 154-248 days). Among 119 patients (85.6%) fully vaccinated for SARS-CoV-2, 86 (61.9% of all) underwent 2 doses while 33 (23.7% of all) received 3 doses. For the outcome of pyrexia and/or dyspnea (N = 40, 28.8%), multivariate analysis showed that significant risk factors were pre-infusion lowered oximetry below 96.5% (Odds Ratio [OR] 0.344, 95% Confidence Interval [CI] 0.139-0.851, P = 0.021) and pre-infusion temperature more than 36.7 degrees Celsius (OR 4.056, 95% CI 1.696-9.701, P = 0.002). Infusion-related reactions included vomiting immediately after infusion, chill/shivering, dizziness, rash, pruritus, pyrexia, and dyspnea. The number of patients with any of these events was 44 (31.6%). Three patients (2.2%) showed worsening of COVID-19; one developed hypoxia and two died. Limitations for this study included no genome typing whether BA.1 or BA.2 lineage of the Omicron variant but the local epidemiology indicated the prevalence of BA.1. Another was sotrovimab administration for inpatients that allow precise detection of post-infusion events, confounding previous exacerbation definition including hospitalization. CONCLUSIONS: For 24 h after infusion of sotrovimab, COVID-19 patients showing pre-infusion lowered oximetry below 96.5% and/or temperature more than 36.7 degrees Celsius may have temperature elevation or dyspnea, warranting close monitoring for these risk factors.

Survey on the current status of the indication and implementation protocols for bile replacement in patients with external biliary drainage with special reference to infection control.

PURPOSE: This survey of bile replacement (BR) was conducted on patients with external biliary drainage to assess the current status of indication and implementation protocol of BR with special reference to infection control. METHODS: A 12-item questionnaire regarding the performance of perioperative BR was sent to 124 institutions in Japan. RESULTS: BR was performed in 29 institutions, and the indication protocol was introduced in 19. BR was performed preoperatively in 11 institutions, pre- and postoperatively in 12, and postoperatively in 6. The methods used for BR administration included oral intake (n = 10), nasogastric tube (n = 1), enteral nutrition tube (n = 3), oral intake and enteral nutrition tube (n = 6), oral intake or nasogastric tube (n = 2), nasogastric tube and enteral nutrition tube (n = 2), and oral intake or nasogastric tube and enteral nutrition tube (n = 5). In 10 of 29 institutions, isolation of multidrug-resistant organisms and a high bacterial load were considered contraindications for the use of BR. Seven institutions experienced environmental contamination. CONCLUSIONS: Given the different implementation of BR among institutions, the appropriate indication and protocols for BR should be established for infection control.

HOMO-LUMO Energy-Gap Tuning of π-Conjugated Zwitterions Composed of Electron-Donating Anion and Electron-Accepting Cation.

π-Conjugated molecules with small highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy gaps (ΔEH-L) have been extensively studied because of their unique optoelectronic properties. Although the expansion of π-conjugation is one of the well-known approaches for designing molecules with small ΔEH-L values, such an approach inevitably gives large π-conjugated molecules sometimes suffering from synthetic difficulty and low solubility toward organic solvents. To develop relatively small donor-acceptor molecules with small ΔEH-L values, we have designed and synthesized π-conjugated zwitterions composed of electron-donating anions, such as phenoxide and anthroxide, and electron-accepting cations, such as pyridinium and acridinium. The energy difference between the HOMO of the anion and the LUMO of the cation (ΔED-A) and the interplanar angle between them (φDA) have a crucial effect on ΔEH-L, and hence, on the electronic structures and optoelectronic properties of these zwitterions. The zwitterions with small ΔED-A and large φDA have a small ΔEH-L of ca. 1 eV and show amphoteric redox properties and near-infrared (NIR) electronic absorption exceeding λ = 1000 nm. The NIR absorption responds to solvent polarity, temperature, and acid addition. This molecular design will generate small π-conjugated donor-acceptor molecules with small ΔEH-L values.

Mortality related to drug-resistant organisms in surgical sepsis-3: an 8-year time trend study using sequential organ failure assessment scores.

The difference in sequential organ failure assessment (SOFA) scores from the baseline to sepsis is a known predictor of sepsis-3 outcome, but the prognostic value of drug-resistant organisms for mortality is unexplained. We employed sepsis stewardship and herein report an observational study. Study subjects were patients admitted to the Departments of Surgery/Chest Surgery from 2011 through 2018 with a diagnosis of sepsis and a SOFA score of 2 or more. Our sepsis stewardship methods included antimicrobial and diagnostic stewardship and infection control. We determined the primary endpoint as in-hospital death and the secondary endpoint as the annual trend of the risk-adjusted mortality ratio (RAMR). For mortality, we performed logistic regression analysis based on SOFA score, age, sex, comorbid disease, and the presence of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase inhibitor-producing bacteria. In a total of 457 patients, two factors were significant predictors for fatality, i.e., SOFA score of 9 or more with an odds ratio (OR) 4.921 and 95% confidence interval [95% CI] 1.968-12.302 (P = 0.001) and presence of MRSA with an OR 1.83 and 95% CI 1.003-3.338 (P = 0.049). RAMR showed a decrease during the study years (P < 0.05). Early detection of MRSA may help patients survive surgical sepsis-3. Thus, MRSA-oriented diagnosis may play a role in expediting treatment with anti-MRSA antimicrobials.

Prognostic relevance of elevated plasma osmolality on admission in acute decompensated heart failure with preserved ejection fraction: insights from PURSUIT-HFpEF registry.

BACKGROUND: Complicated pathophysiology makes it difficult to identify the prognosis of heart failure with preserved ejection fraction (HFpEF). While plasma osmolality has been reported to have prognostic importance, mainly in heart failure with reduced ejection fraction (HFrEF), its prognostic meaning for HFpEF has not been elucidated. METHODS: We prospectively studied 960 patients in PURSUIT-HFpEF, a multicenter observational study of acute decompensated HFpEF inpatients. We divided patients into three groups according to the quantile values of plasma osmolality on admission. During a follow-up averaging 366 days, we examined the primary composite endpoint of cardiac mortality or heart failure re-admission using Kaplan-Meier curve analysis and Cox proportional hazard testing. RESULTS: 216 (22.5%) patients reached the primary endpoint. Kaplan-Meier curve analysis revealed that the highest quantile of plasma osmolality on admission (higher than 300.3 mOsm/kg) was significantly associated with adverse outcomes (Log-rank P = 0.0095). Univariable analysis in the Cox proportional hazard model also revealed significantly higher rates of adverse outcomes in the higher plasma osmolality on admission (hazard ratio [HR] 7.29; 95% confidence interval [CI] 2.25-23.92, P = 0.0009). Multivariable analysis in the Cox proportional hazard model also showed that higher plasma osmolality on admission was significantly associated with adverse outcomes (HR 5.47; 95% CI 1.46-21.56, P = 0.0113) independently from other confounding factors such as age, gender, comorbid of atrial fibrillation, hypertension history, diabetes, anemia, malnutrition, E/e', and N-terminal pro-B-type natriuretic peptide elevation. CONCLUSIONS: Higher plasma osmolality on admission was prognostically important for acute decompensated HFpEF inpatients.

Ipsilateral-Dominant Control of Limb Movements in Rodent Posterior Parietal Cortex.

It is well known that the posterior parietal cortex (PPC) and frontal motor cortices in primates preferentially control voluntary movements of contralateral limbs. The PPC of rats has been defined based on patterns of thalamic and cortical connectivity. The anatomical characteristics of this area suggest that it may be homologous to the PPC of primates. However, its functional roles in voluntary forelimb movements have not been well understood, particularly in the lateralization of motor limb representation; that is, the limb-specific activity representations for right and left forelimb movements. We examined functional spike activity of the PPC and two motor cortices, the primary motor cortex (M1) and the secondary motor cortex (M2), when head-fixed male rats performed right or left unilateral movements. Unlike primates, PPC neurons in rodents were found to preferentially represent ipsilateral forelimb movements, in contrast to the contralateral preference of M1 and M2 neurons. Consistent with these observations, optogenetic activation of PPC and motor cortices, respectively, evoked ipsilaterally and contralaterally biased forelimb movements. Finally, we examined the effects of optogenetic manipulation on task performance. PPC or M1 inhibition by optogenetic GABA release shifted the behavioral limb preference contralaterally or ipsilaterally, respectively. In addition, weak optogenetic PPC activation, which was insufficient to evoke motor responses by itself, shifted the preference ipsilaterally; although similar M1 activation showed no effects on task performance. These paradoxical observations suggest that the PPC plays evolutionarily different roles in forelimb control between primates and rodents.SIGNIFICANCE STATEMENT In rodents, the primary and secondary motor cortices (M1 and M2, respectively) are involved in voluntary movements with contralateral preference. However, it remains unclear whether and how the posterior parietal cortex (PPC) participates in controlling multiple limb movements. We recorded functional activity from these areas using a behavioral task to monitor movements of the right and left forelimbs separately. PPC neurons preferentially represented ipsilateral forelimb movements and optogenetic PPC activation evoked ipsilaterally biased forelimb movements. Optogenetic PPC inhibition via GABA release shifted the behavioral limb preference contralaterally during task performance, whereas weak optogenetic PPC activation, which was insufficient to evoke motor responses by itself, shifted the preference ipsilaterally. Our findings suggest rodent PPC contributes to ipsilaterally biased motor response and/or planning.

A spike analysis method for characterizing neurons based on phase locking and scaling to the interval between two behavioral events.

Standard analysis of neuronal functions assesses the temporal correlation between animal behaviors and neuronal activity by aligning spike trains with the timing of a specific behavioral event, e.g., visual cue. However, spike activity is often involved in information processing dependent on a relative phase between two consecutive events rather than a single event. Nevertheless, less attention has so far been paid to such temporal features of spike activity in relation to two behavioral events. Here, we propose "Phase-Scaling analysis" to simultaneously evaluate the phase locking and scaling to the interval between two events in task-related spike activity of individual neurons. This analysis method can discriminate conceptual "scaled"-type neurons from "nonscaled"-type neurons using an activity variation map that combines phase locking with scaling to the interval. Its robustness was validated by spike simulation using different spike properties. Furthermore, we applied it to analyzing actual spike data from task-related neurons in the primary visual cortex (V1), posterior parietal cortex (PPC), primary motor cortex (M1), and secondary motor cortex (M2) of behaving rats. After hierarchical clustering of all neurons using their activity variation maps, we divided them objectively into four clusters corresponding to nonscaled-type sensory and motor neurons and scaled-type neurons including sustained and ramping activities, etc. Cluster/subcluster compositions for V1 differed from those of PPC, M1, and M2. The V1 neurons showed the fastest functional activities among those areas. Our method was also applicable to determine temporal "forms" and the latency of spike activity changes. These findings demonstrate its utility for characterizing neurons.NEW & NOTEWORTHY Phase-Scaling analysis is a novel technique to unbiasedly characterize the temporal dependency of functional neuron activity on two behavioral events and objectively determine the latency and form of the activity change. This powerful analysis can uncover several classes of latently functioning neurons that have thus far been overlooked, which may participate differently in intermediate processes of a brain function. The Phase-Scaling analysis will yield profound insights into neural mechanisms for processing internal information.

A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.

BACKGROUND: Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS: We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS: In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, -10.1 percentage points; 95% confidence interval [CI], -15.9 to -4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, -9.9 percentage points; 95% CI, -15.5 to -4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, -11.6 percentage points; 95% CI, -17.4 to -5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, -10.7 percentage points; 95% CI, -16.4 to -5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS: Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239 .).

Metal-Free Twofold Electrochemical C-H Amination of Activated Arenes: Application to Medicinally Relevant Precursor Synthesis.

The efficient production of many medicinally or synthetically important starting materials suffers from wasteful or toxic precursors for the synthesis. In particular, the aromatic non-protected primary amine function represents a versatile synthetic precursor, but its synthesis typically requires toxic oxidizing agents and transition metal catalysts. The twofold electrochemical amination of activated benzene derivatives via Zincke intermediates provides an alternative sustainable strategy for the formation of new C-N bonds of high synthetic value. As a proof of concept, we use our approach to generate a benzoxazinone scaffold that gained attention as a starting structure against castrate-resistant prostate cancer. Further improvement of the structure led to significantly increased cancer cell line toxicity. Thus, exploiting environmentally benign electrooxidation, we present a new versatile and powerful method based on direct C-H activation that is applicable for example the production of medicinally relevant compounds.

Electrogenerated Cationic Reactive Intermediates: The Pool Method and Further Advances.

Electrochemistry serves as a powerful method for generating reactive intermediates, such as organic cations. In general, there are two ways to use reactive intermediates for chemical reactions: (1) generation in the presence of a reaction partner and (2) generation in the absence of a reaction partner with accumulation in solution as a "pool" followed by reaction with a subsequently added reaction partner. The former approach is more popular because reactive intermediates are usually short-lived transient species, but the latter method is more flexible and versatile. This review focuses on the latter approach and provides a concise overview of the current methods for the generation and accumulation of cationic reactive intermediates as a pool using modern techniques of electrochemistry and their reactions with subsequently added nucleophilic reaction partners.

A Novel Approach to Functionalization of Aryl Azides through the Generation and Reaction of Organolithium Species Bearing Masked Azides in Flow Microreactors.

A novel straightforward method for aryl azides having functional groups based on generation and reactions of aryllithiums bearing a triazene group from polybromoarenes using flow microreactor systems was achieved. The present approach will serve as a powerful method in organolithium chemistry and open a new possibility in the synthesis of polyfunctional organic azides.

Oxo-Thiolation of Cationically Polymerizable Alkenes Using Flow Microreactors.

The present study describes the cationic oxo-thiolation of polymerizable alkenes by using highly reactive cationic species generated by anodic oxidation. These highly reactive cations were able to activate alkenes before their polymerization. Fast mixing in flow microreactors effectively controlled chemoselectivity, enabling higher reaction temperatures.

Generation and Reaction of Functional Alkyllithiums by Using Microreactors and Their Application to Heterotelechelic Polymer Synthesis.

Flow microreactors enabled the successful generation of various functional alkyllithiums containing electrophilic functional groups, as well as the use of these alkyllithiums in subsequent reactions. The high reactivity of these series of reactions could be achieved by the extremely accurate and selective control of residence time. Moreover, integrated flow microreactor systems could be used to successfully synthesize heterotelechelic polymers with two functionalities, one at each end, via a process involving controlled anionic polymerization initiated by functional alkyllithium compounds, followed by trapping reactions with difunctional electrophiles.

Synthesis of Functionalized Ketones from Acid Chlorides and Organolithiums by Extremely Fast Micromixing.

Synthesis of ketones containing various functional groups from acid chlorides bearing electrophilic functional groups and functionalized organolithiums was achieved using a flow microreactor system. Extremely fast mixing is important for high chemoselectivity.

In Vivo Spiking Dynamics of Intra- and Extratelencephalic Projection Neurons in Rat Motor Cortex.

In motor cortex, 2 types of deep layer pyramidal cells send their axons to other areas: intratelencephalic (IT)-type neurons specifically project bilaterally to the cerebral cortex and striatum, whereas neurons of the extratelencephalic (ET)-type, termed conventionally pyramidal tract-type, project ipsilaterally to the thalamus and other areas. Although they have totally different synaptic and membrane potential properties in vitro, little is known about the differences between them in ongoing spiking dynamics in vivo. We identified IT-type and ET-type neurons, as well as fast-spiking-type interneurons, using novel multineuronal analysis based on optogenetically evoked spike collision along their axons in behaving/resting rats expressing channelrhodopsin-2 (Multi-Linc method). We found "postspike suppression" (~100 ms) as a characteristic of ET-type neurons in spike auto-correlograms, and it remained constant independent of behavioral conditions in functionally different ET-type neurons. Postspike suppression followed even solitary spikes, and spike bursts significantly extended its duration. We also observed relatively strong spike synchrony in pairs containing IT-type neurons. Thus, spiking dynamics in IT-type and ET-type neurons may be optimized differently for precise and coordinated motor control.