The type of inhibition provided by thalamic interneurons alters the input selectivity of thalamocortical neurons.

A fundamental problem in neuroscience is how neurons select for their many inputs. A common assumption is that a neuron's selectivity is largely explained by differences in excitatory synaptic input weightings. Here we describe another solution to this important problem. We show that within the first order visual thalamus, the type of inhibition provided by thalamic interneurons has the potential to alter the input selectivity of thalamocortical neurons. To do this, we developed conductance injection protocols to compare how different types of synchronous and asynchronous GABA release influence thalamocortical excitability in response to realistic patterns of retinal ganglion cell input. We show that the asynchronous GABA release associated with tonic inhibition is particularly efficient at maintaining information content, ensuring that thalamocortical neurons can distinguish between their inputs. We propose a model where alterations in GABA release properties results in rapid changes in input selectivity without requiring structural changes in the network.

Photocatalytic Z/E isomerization unlocking the stereodivergent construction of axially chiral alkene frameworks.

The past century has witnessed a large number of reports on the Z/E isomerization of alkenes. However, the vast majority of them are still limited to the isomerization of di- and tri-substituted alkenes. The stereospecific Z/E isomerization of tetrasubstituted alkenes remains to be an underdeveloped area, thus lacking in a stereodivergent synthesis of axially chiral alkenes. Herein we report the atroposelective synthesis of tetrasubstituted alkene analogues by asymmetric allylic substitution-isomerization, followed by their Z/E isomerization via triplet energy transfer photocatalysis. In this regard, the stereodivergent synthesis of axially chiral N-vinylquinolinones is achieved efficiently. Mechanistic studies indicate that the benzylic radical generation and distribution are two key factors for preserving the enantioselectivities of axially chiral compounds.

The mode and timing of administrating nutritional treatment of critically ill elderly patients in intensive care units: a multicenter prospective study.

Introduction: Critically ill patients are more susceptible to malnutrition due to their severe illness. Moreover, elderly patients who are critically ill lack specific nutrition recommendations, with nutritional care in the intensive care units (ICUs) deplorable for the elderly. This study aims to investigate nutrition treatment and its correlation to mortality in elderly patients who are critically ill in intensive care units. Method: A multiple-center prospective cohort study was conducted in China from 128 intensive care units (ICUs). A total of 1,238 elderly patients were included in the study from 26 April 2017. We analyzed the nutrition characteristics of elderly patients who are critically ill, including initiated timing, route, ways of enteral nutrition (EN), and feeding complications, including the adverse aspects of feeding, acute gastrointestinal injury (AGI), and feeding interruption. Multivariate logistic regression analysis was used to screen out the impact of nutrition treatment on a 28-day survival prognosis of elderly patients in the ICU. Result: A total of 1,238 patients with a median age of 76 (IQR 70-83) were enrolled in the study. The Sequential Organ Failure (SOFA) median score was 7 (interquartile range: IQR 5-10) and the median Acute Physiology and Chronic Health Evaluation (APACHE) II was 21 (IQR 16-25). The all-cause mortality score was 11.6%. The percentage of nutritional treatment initiated 24 h after ICU admission was 58%, with an EN of 34.2% and a parenteral nutrition (PN) of 16.0% in elderly patients who are critically ill. Patients who had gastrointestinal dysfunction with AGI stage from 2 to 4 were 25.2%. Compared to the survivors' group, the non-survivors group had a lower ratio of EN delivery (57% vs. 71%; p = 0.015), a higher ratio of post-pyloric feeding (9% vs. 2%; p = 0.027), and higher frequency of feeding interrupt (24% vs. 17%, p = 0.048). Multivariable logistics regression analysis showed that patients above 76 years old with OR (odds ratio) 2.576 (95% CI, 1.127-5.889), respiratory rate > 22 beats/min, and ICU admission for 24 h were independent risk predictors of the 28-day mortality study in elderly patients who are critically ill. Similarly, other independent risk predictors of the 28-day mortality study were those with an OR of 2.385 (95%CI, 1.101-5.168), lactate >1.5 mmol/L, and ICU admission for 24 h, those with an OR of 7.004 (95%CI, 2.395-20.717) and early PN delivery within 24 h of ICU admission, and finally those with an OR of 5.401 (95%CI, 1.175-24.821) with EN delivery as reference. Conclusion: This multi-center prospective study describes clinical characteristics, the mode and timing of nutrition treatment, frequency of AGI, and adverse effects of nutrition in elderly ICU patients. According to this survey, ICU patients with early PN delivery, older age, faster respiratory rate, and higher lactate level may experience poor prognosis.

Inhibition of the glutamatergic PVT-NAc projections attenuates local anesthetic-induced neurotoxic behaviors.

INTRODUCTION: Local anesthetic-induced neurotoxicity contributes to perioperative nerve damage; however, the underlying mechanisms remain unclear. Here, we investigated the role of the paraventricular thalamus (PVT)-nucleus accumbens (NAc) projections in neurotoxicity induced by ropivacaine, a local anesthetic agent. METHODS: Ropivacaine (58 mg/kg, intraperitoneal administration) was used to construct the local anesthetic systemic toxicity (LAST) mice model. We first identified neural projections from the PVT to the NAc through the expression of a retrograde tracer and virus. The inhibitory viruses (rAAV-EF1α-DIO-hm4D(Gi)-mCherry-WPREs: AAV2/retro and rAAV-CaMKII-CRE-WPRE-hGh: AAV2/9) were injected into the mice model to assess the effects of the specific inhibition of the PVT-NAc pathway on neurological behaviors in the presence of clozapine-N-oxide. The inhibition of the PVT-NAc pathway was evaluated by immunofluorescence staining of c-Fos-positive neurons and Ca2+ signals in CaMKIIa neurons. RESULTS: We successfully identified a circuit connecting the PVT and NAc in C57BL/6 mice. Ropivacaine administration induced the activation of the PVT-NAc pathway and seizures. Specific inhibition of NAc-projecting CaMKII neurons in the PVT was sufficient to inhibit the neuronal activity in the NAc, which subsequently decreased ropivacaine-induced neurotoxicity. CONCLUSION: These results reveal the presence of a dedicated PVT-NAc circuit that regulates local anesthetic-induced neurotoxicity and provide a potential mechanistic explanation for the treatment and prevention of LAST.

High-Density Energetic Materials with Low Mechanical Sensitivity and Twinning Derived from Nitroimidazole Fused Ring.

The innovative synthesis of 3,8-dibromo-2,9-dinitro-5,6-dihydrodiimidazo [1,2-a:2',1'-c]pyrazine and 3,9-dibromo-2,10-dinitro-6,7-dihydro-5H-diimidazo [1,2-a:2',1'-c][1,4]diazepine is described in this study. The tricyclic fused molecular structures are formed by the respective amalgamation of piperazine and homopiperazine with the imidazole ring containing nitro. Compound 1 and 2 possess excellent high-density physical properties (ρ1 = 2.49 g/cm3, ρ2 = 2.35 g/cm3) due to the presence of a fused ring structure and Br atom. In addition to their high density, they have high decomposition temperatures (Td > 290 °C) which means that they have excellent thermal stability and can be used as potential heat-resistant explosives. Low mechanical sensitivities (IS > 40 J, FS > 360 N) are observed. The twinning structure of 2 was resolved by X-ray diffraction. Non-covalent interaction analysis, Hirshfeld surfaces, 2D fingerprint plot, and Electrostatic potential analysis were used to understand the intramolecular interactions in relation to physicochemical properties. The unique structures of this type of compound provide new potential for the evolution of energetic materials.

Ultra-high density electrodes improve detection, yield, and cell type identification in neuronal recordings.

To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single neuron and single spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra (NP Ultra). This device samples neuronal activity at ultra-high spatial density (~10 times higher than previous probes) with low noise levels, while trading off recording span. NP Ultra is effectively an implantable voltage-sensing camera that captures a planar image of a neuron's electrical field. We use a spike sorting algorithm optimized for these probes to demonstrate that the yield of visually-responsive neurons in recordings from mouse visual cortex improves up to ~3-fold. We show that NP Ultra can record from small neuronal structures including axons and dendrites. Recordings across multiple brain regions and four species revealed a subset of extracellular action potentials with unexpectedly small spatial spread and axon-like features. We share a large-scale dataset of these brain-wide recordings in mice as a resource for studies of neuronal biophysics. Finally, using ground-truth identification of three major inhibitory cortical cell types, we found that these cell types were discriminable with approximately 75% success, a significant improvement over lower-resolution recordings. NP Ultra improves spike sorting performance, detection of subcellular compartments, and cell type classification to enable more powerful dissection of neural circuit activity during behavior.

DREDge: robust motion correction for high-density extracellular recordings across species.

High-density microelectrode arrays (MEAs) have opened new possibilities for systems neuroscience in human and non-human animals, but brain tissue motion relative to the array poses a challenge for downstream analyses, particularly in human recordings. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm which is well suited for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from spikes in the action potential (AP) frequency band, DREDge enables automated tracking of motion at high temporal resolution in the local field potential (LFP) frequency band. In human intraoperative recordings, which often feature fast (period <1s) motion, DREDge correction in the LFP band enabled reliable recovery of evoked potentials, and significantly reduced single-unit spike shape variability and spike sorting error. Applying DREDge to recordings made during deep probe insertions in nonhuman primates demonstrated the possibility of tracking probe motion of centimeters across several brain regions while simultaneously mapping single unit electrophysiological features. DREDge reliably delivered improved motion correction in acute mouse recordings, especially in those made with an recent ultra-high density probe. We also implemented a procedure for applying DREDge to recordings made across tens of days in chronic implantations in mice, reliably yielding stable motion tracking despite changes in neural activity across experimental sessions. Together, these advances enable automated, scalable registration of electrophysiological data across multiple species, probe types, and drift cases, providing a stable foundation for downstream scientific analyses of these rich datasets.

Asymmetric Allylic Substitution-Isomerization for the Modular Synthesis of Axially Chiral N-Vinylquinazolinones.

Axially chiral N-substituted quinazolinones are important bioactive molecules, which are presented in many synthetic drugs. However, most strategies toward their atroposelective synthesis are mainly limited to the axially chiral arylquinazolinone frameworks. The development of modular synthetic methods to access diverse quinazolinone-based atropisomers remains scarce and challenging. Herein, we report the regio- and atroposelective synthesis of axially chiral N-vinylquinazolinones via the strategy of asymmetric allylic substitution-isomerization. The catalysis system utilized both asymmetric transition-metal catalysis and organocatalysis to efficiently afford trisubstituted and tetrasubstituted N-vinylquinazolinone atropisomers, respectively. With the meticulous design of ß-substituted allylic substrates, both Z- and E-tetrasubstituted axially chiral N-vinylquinazolinones were obtained in good yields and high enantioselectivities.

Design and Synthesis of Bistetrazole-Based Energetic Salts Bearing the Nitrogen-Rich Fused Ring.

A series of bistetrazole-based energetic salts bearing a nitrogen-rich fused ring were designed and synthesized. Among them, compounds 4-10 showed good detonation properties and excellent thermostability. By treating nitrogen-rich fused ring 3 with concentrated hydrochloric acid, a new type of Dimroth rearrangement was observed that afforded compound 12 efficiently. This new transformation herein constitutes a valuable addition to the Dimroth rearrangement.

Effect of ß-blockers on mortality in patients with sepsis: A propensity-score matched analysis.

Objectives: We aimed to evaluate the association between ß-blocker therapy and mortality in patients with sepsis. Methods: Patients with sepsis were selected from the Medical Information Mart for Intensive Care (MIMIC)-III. Propensity score matching (PSM) was used to balance the baseline differences. A multivariate Cox regression model was used to assess the relationship between ß-blocker therapy and mortality. The primary outcome was the 28-day mortality. Results: A total of 12,360 patients were included in the study, involving 3,895 who received ß-blocker therapy and 8,465 who did not. After PSM, 3,891 pairs of patients were matched. The results showed that ß-blockers were associated with improved 28- (hazards ratio (HR) 0.78) and 90-day (HR 0.84) mortality. Long-acting ß-blockers were associated with improved 28-day survival (757/3627 [20.9%] vs. 583/3627 [16.1%], P < 0.001, HR0.76) and 90-day survival (1065/3627 [29.4%] vs.921/3627 [25.4%], P < 0.001, HR 0.77). Short-acting ß-blocker treatment did not reduce the 28-day and 90-day mortality (61/264 [23.1%] vs. 63/264 [23.9%], P = 0.89 and 83/264 [31.4%] vs. 89/264 [31.7%], P = 0.8, respectively). Conclusions: ß-blockers were associated with improved 28- and 90-day mortality in patients with sepsis and septic shock. Long-acting ß-blocker therapy may have a protective role in patients with sepsis, reducing the 28-day and 90-day mortality. However, short-acting ß-blocker (esmolol) treatment did not reduce the mortality in sepsis.

Combination of Energetic Tetrazole and Triazole: Promising Materials with Exceptional Stability and Low Mechanical Sensitivity as Propellants and Gas Generators.

An innovative synthesis of 5-((1H-tetrazol-5-yl)methyl)-4H-1,2,4-triazole-3,4-diamine (TMT) based on triazole and tetrazole frameworks bearing double amino groups was reported. It is worth mentioning that TMT is insensitive to impact and friction (IS > 40 J, FS > 360 N), thus enabling it to have an exceptional thermal decomposition behavior that is superior to RDX and TNT. Meanwhile, it also has relatively high energetic performance (Dv = 8.417 km/s). A series of energy-containing salts TMT-1-8 were also investigated for their potential applications. Except for TMT-4 and TMT-7, the remaining nitrogen-rich salts have initial decomposition temperatures above 200 °C. Furthermore, the salts with positive heat generation all have extraordinary gas production, especially for TMT-1 (Vo = 840.5 dm3/kg), TMT-2 (Vo = 803.9 dm3/kg), and TMT-7 (Vo = 844.3 dm3/kg). The low mechanical sensitivities of the TMT series were discovered, and a majority of them have impact sensitivities exceeding 40 J with friction sensitivities exceeding 360 N which are superior to TNT (IS = 15 J, FS = 353 N). The intermolecular and intramolecular interactions of the crystals TMT-1-3 were explored by Hirshfeld surfaces, 2D fingerprint plots, noncovalent interaction (NCI) analysis, and electrostatic potential surface analysis to understand the physicochemical property changes in relation to the structure. Consequently, this novel tri/tetrazole and polyamine system as a promising material provides the impetus for the development of gas generators and propellants.

Quantitative analysis of rabies virus-based synaptic connectivity tracing.

Monosynaptically restricted rabies viruses have been used for more than a decade for synaptic connectivity tracing. However, the verisimilitude of quantitative conclusions drawn from these experiments is largely unknown. The primary reason is the simple metrics commonly used, which generally disregard the effect of starter cell numbers. Here we present an experimental dataset with a broad range of starter cell numbers and explore their relationship with the number of input cells across the brain using descriptive statistics and modelling. We show that starter cell numbers strongly affect input fraction and convergence index measures, making quantitative comparisons unreliable. Furthermore, we suggest a principled way to analyse rabies derived connectivity data by taking advantage of the starter vs input cell relationship that we describe and validate across independent datasets.

Effect of basal metabolic rate on osteoporosis: A Mendelian randomization study.

Purpose: Basal metabolic rate may play a key role in the pathogenesis and progression of osteoporosis. We performed Mendelian random analysis to evaluate the causal relationship between basal metabolic rate and osteoporosis. Methods: Instrumental variables for the basal metabolic rate were selected. We used the inverse variance weighting approach as the main Mendelian random analysis method to estimate causal effects based on the summary-level data for osteoporosis from genome-wide association studies. Results: A potential causal association was observed between basal metabolic rate and risks of osteoporosis (odds ratio = 0.9923, 95% confidence interval: 0.9898-0.9949; P = 4.005e - 09). The secondary MR also revealed that BMR was causally associated with osteoporosis (odds ratio = 0.9939, 95% confidence interval: 0.9911-0.9966; P = 1.038e - 05). The accuracy and robustness of the findings were confirmed using sensitivity tests. Conclusion: Basal metabolic rate may play a causal role in the development of osteoporosis, although the underlying mechanisms require further investigation.

Ultrahigh-Loaded Fe Single Atoms and Fe3C Nanoparticle Catalysts as Air Cathodes for High-Performance Zn-Air Batteries.

Fe-based materials containing Fe-Nx sites have emerged as promising electrocatalysts in the oxygen reduction reaction (ORR), but they still suffer structural instability which may lead to loss of catalytic activity. Herein, a novel electrocatalyst Fe3C-FeSA@3DCN with the coexistence of Fe3C nanoparticles and Fe single atoms (FeSA) in a three-dimensional conductive network (3DCN) is prepared via lattice confinement and defect trapping strategies with an Fe atomic loading of as high as 4.36%. In the ORR process, the limiting current density of Fe3C-FeSA@3DCN reaches 5.72 mA cm-2, with an onset potential of 0.926 V and a Tafel slope of 66 mV/decade, showing better catalytic activity and stability than Pt/C catalysts. Notably, its assembled aqueous and solid-state Zn-air batteries (ZABs) achieve peak power densities of 166 and 56 mW cm-2, respectively, with a long service life of up to 200 h at a current density of 5 mA cm-2. In addition, the assembled ZAB can provide a constant voltage on activated carbon electrodes to perform capacitive deionization to adsorb different ions. The importance of the Fe species active sites generated by Fe3C and FeSA in the material for ORR activity to boost the electron transfer and mass transfer is demonstrated by a simple selective poisoning experiment.

Association between albumin infusion and septic patients with coronary heart disease: A retrospective study based on medical information mart for intensive care III database.

Coronary heart disease (CHD) is a common comorbidity in intensive care unit (ICU) patients, particularly in the elderly. This particular population may have worse conditions during sepsis, and it presents an overwhelming challenge for clinical practice. Previous studies suggested that patients with CHD have an increased risk of cardiovascular events, and low albumin concentration worsens the prognosis of patients with stable CHD. Hypoalbuminemia in patients with sepsis is common due to nutritional disorders, excessive consumption, and leakage. Albumin is a fluid often used for resuscitation in patients with sepsis. However, albumin infusion in patients with sepsis and CHD has rarely been studied. The effects and safety of albumin infusion in patients with sepsis and CHD remain unclear. Therefore, we collected medical information from Mimic-III (Mimic-III) and compared the all-cause mortality and cardiovascular mortality at 28- or 90-day between the albumin and non-albumin groups in septic patients with CHD. A total of 2,027 patients with sepsis and CHD were included in our study, with 405 in the albumin group and 1,622 in the non-albumin group. After propensity score matching (PSM), 350 pairs were included in our study. Improved survival benefits were found in the albumin group at the 28-day all-cause mortality compared with the non-albumin group (hazard ratio [HR], 0.54; 95% CI: 0.38-0.78; p = 0.0009). However, no difference was detected in the 90-day survival benefits (HR, 0.80, 95% CI: 0.60-1.06, p = 0.1207). Albumin infusion did not reverse cardiovascular mortality neither at 28th day nor at 90th day (cardiovascular mortality: 28 days, HR, 0.52, 95% CI: 0.23-1.19, p = 0.1218; 90 days, HR, 0.66, 95% CI: 0.33-1.33, p = 0.2420).

Stepwise Asymmetric Allylic Substitution-Isomerization Enabled Mimetic Synthesis of Axially Chiral B,N-Heterocycles.

Axially chiral molecules bearing multiple stereogenic axes are of great importance in the field of organic chemistry. However, the efficient construction of atropisomers featuring two different types of stereogenic axes has rarely been explored. Herein, we report the novel atroposelective synthesis of configurationally stable axially chiral B,N-heterocycles. By using stepwise asymmetric allylic substitution-isomerization (AASI) strategy, diaxially chiral B,N-heterocycles bearing B-C and C-N axes that are related to the moieties of axially chiral enamines and arylborons were also obtained. In this case, all four stereoisomers of diaxially chiral B,N-heterocycles were stereodivergently afforded in high enantioselectivities. Density functional theory (DFT) studies demonstrated that the NH⋅⋅⋅π interactions played a unique role in the promotion of stereospecific isomerization, thereby leading to the highly efficient central-to-axial chirality transfer.

Machine learning for early prediction of sepsis-associated acute brain injury.

Background: Sepsis-associated encephalopathy (SAE) is defined as diffuse brain dysfunction associated with sepsis and leads to a high mortality rate. We aimed to develop and validate an optimal machine-learning model based on clinical features for early predicting sepsis-associated acute brain injury. Methods: We analyzed adult patients with sepsis from the Medical Information Mart for Intensive Care (MIMIC III) clinical database. Candidate models were trained using random forest, support vector machine (SVM), decision tree classifier, gradients boosting machine (GBM), multiple layer perception (MLP), extreme gradient boosting (XGBoost), light gradients boosting machine (LGBM) and a conventional logistic regression model. These methods were applied to develop and validate the optimal model based on its accuracy and area under curve (AUC). Results: In total, 12,460 patients with sepsis met inclusion criteria, and 6,284 (50.4%) patients suffered from sepsis-associated acute brain injury. Compared other models, the LGBM model achieved the best performance. The AUC for both train set and test set indicated excellent validity (Trainset AUC 0.91, Testset AUC 0.87). Feature importance analysis showed that glucose, age, mean arterial pressure, heart rate, hemoglobin, and length of ICU stay were the top 6 important clinical factors to predict occurrence of sepsis-associated acute brain injury. Conclusion: Almost half of patients admitted to ICU with sepsis had sepsis-associated acute brain injury. The LGBM model better identify patients with sepsis-associated acute brain injury than did other machine-learning models. Glucose, age, and mean arterial pressure were the three most important clinical factors to predict occurrence of sepsis-associated acute brain injury.

ZIF-8-derived N-doped porous carbon wrapped in porous carbon films as an air cathode for flexible solid-state Zn-air batteries.

Metal-organic frameworks are a new type of catalyst precursor with high specific surface area and controllable composition, which can be modified by post-treatment and are suitable for use as cathode catalysts for Zn-air batteries (ZABs). Here, a self-doped nitrogen nanocatalyst (N-PC@CF) with a double-layered porous structure is rationally designed for flexible solid-state ZABs. The outer porous carbon shell of the N-PC@CF is highly hydrophilic and O2 permeable, while the layered porous structure exposes sufficient active sites to shorten the mass transfer distance, which would promote electrocatalytic performance and increase flexibility efficiently. The obtained N-PC@CF has an onset potential of 0.926 V and a half-wave potential of 0.843 V in the oxygen reduction reaction test, which is equivalent to commercial Pt/C. Most importantly, the maximum power density of the assembled ZAB is 134.7 mW cm-2 and it exhibits a specific capacity of 776.8 mA h g-1 at 10 mA cm-2, which is better than the 99.9 mW cm-2 of the Pt/C-based battery. An obvious improvement in the constant current discharge-charge cycle durability of the ZAB is found when compared with Pt/C. The specific capacities of ZAB with N-PC@CF as the air cathode at 5, 10 and 15 mA cm-2 are 842.7, 776.8 and 715.0 mAh g-1 (calculated by the mass of zinc consumed), respectively, corresponding to high energy densities of 1089.7, 977.3 and 842.2 Wh kg-1. A flexible solid-state battery is assembled with excellent flexibility and stability, even if the battery is folded into a large angle (160°). This work provides a new strategy for the design and synthesis of metal-free air cathodes.

Highly sensitive determination of paracetamol, uric acid, dopamine, and catechol based on flexible plastic electrochemical sensors.

Flexible sensing is an alternative to traditional sensing and possesses good flexibility and wearability. Intrinsically conductive polymers, particularly poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS), have received significant attention due to their high mechanical flexibility and good biocompatibility. Here, we report the design of highly conductive and electrochemically active PEDOT:PSS-coated plastic substrate electrodes by combining N-doped graphene (NG) or S-doped graphene (SG) with methanesulfonic acid-treated PEDOT:PSS (denoted as NG-f-MSA-PEDOT:PSS/PET and SG-f-MSA-PEDOT:PSS/PET) by a simple drop-coating method. At room temperature, the NG-f-MSA-PEDOT:PSS/PET electrode demonstrated the lowest detection limits of 17.09, 33.84, 28.30, and 44.96 nM for paracetamol, uric acid, dopamine, and catechol (S/N = 3), respectively. The NG-f-MSA-PEDOT:PSS/PET electrode had good anti-interference ability and reproducibility without employing expensive noble metals and requiring much effort to polish the surface of traditional glass carbon electrodes. Most importantly, this film electrode could maintain a stable electrochemical response under different bending and crease states and had excellent mechanical stability and flexibility.

Dendritic Domain-Specific Sampling of Long-Range Axons Shapes Feedforward and Feedback Connectivity of L5 Neurons.

Feedforward and feedback pathways interact in specific dendritic domains to enable cognitive functions such as predictive processing and learning. Based on axonal projections, hierarchically lower areas are thought to form synapses primarily on dendrites in middle cortical layers, whereas higher-order areas are thought to target dendrites in layer 1 and in deep layers. However, the extent to which functional synapses form in regions of axodendritic overlap has not been extensively studied. Here, we use viral tracing in the secondary visual cortex of male mice to map brain-wide inputs to thick-tufted layer 5 pyramidal neurons. Furthermore, we provide a comprehensive map of input locations through subcellular optogenetic circuit mapping. We show that input pathways target distinct dendritic domains with far greater specificity than appears from their axonal branching, often deviating substantially from the canonical patterns. Common assumptions regarding the dendrite-level interaction of feedforward and feedback inputs may thus need revisiting.SIGNIFICANCE STATEMENT Perception and learning depend on the ability of the brain to shape neuronal representations across all processing stages. Long-range connections across different hierarchical levels enable diverse sources of contextual information, such as predictions or motivational state, to modify feedforward signals. Assumptions regarding the organization of this hierarchical connectivity have not been extensively verified. Here, we assess the synaptic connectivity of brain-wide projections onto pyramidal neurons in the visual cortex of mice. Using trans-synaptic viral tracing and subcellular optogenetic circuit mapping, we show that functional synapses do not follow the consistent connectivity rule predicted by their axonal branching patterns. These findings highlight the diversity of computational strategies operating throughout cortical networks and may aid in building better artificial networks.