Programmable RNA sensing for cell monitoring and manipulation.

RNA is a central and universal mediator of genetic information underlying the diversity of cell types and cell states, which together shape tissue organization and organismal function across species and lifespans. Despite numerous advances in RNA sequencing technologies and the massive accumulation of transcriptome datasets across the life sciences1,2, the dearth of technologies that use RNAs to observe and manipulate cell types remains a bottleneck in biology and medicine. Here we describe CellREADR (Cell access through RNA sensing by Endogenous ADAR), a programmable RNA-sensing technology that leverages RNA editing mediated by ADAR to couple the detection of cell-defining RNAs with the translation of effector proteins. Viral delivery of CellREADR conferred specific cell-type access in mouse and rat brains and in ex vivo human brain tissues. Furthermore, CellREADR enabled the recording and control of specific types of neurons in behaving mice. CellREADR thus highlights the potential for RNA-based monitoring and editing of animal cells in ways that are specific, versatile, simple and generalizable across organ systems and species, with wide applications in biology, biotechnology and programmable RNA medicine.

Genetic dissection of the glutamatergic neuron system in cerebral cortex.

Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon3,4. Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen temporally inducible mouse Cre and Flp knock-in driver lines to enable the combinatorial targeting of major progenitor types and projection classes. Combinatorial strategies confer viral access to subsets of pyramidal neurons defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for understanding the hierarchical organization and developmental trajectory of subpopulations of pyramidal neurons that assemble cortical processing networks and output channels.

Cellular anatomy of the mouse primary motor cortex.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture.

Desloratadine alleviates ALS-like pathology in hSOD1G93A mice via targeting 5HTR2A on activated spinal astrocytes.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive loss of motor neurons in the spinal cord, cerebral cortex and brain stem. ALS is characterized by gradual muscle atrophy and dyskinesia. The limited knowledge on the pathology of ALS has impeded the development of therapeutics for the disease. Previous studies have shown that autophagy and astrocyte-mediated neuroinflammation are involved in the pathogenesis of ALS, while 5HTR2A participates in the early stage of astrocyte activation, and 5HTR2A antagonism may suppress astrocyte activation. In this study, we evaluated the therapeutic effects of desloratadine (DLT), a selective 5HTR2A antagonist, in human SOD1G93A (hSOD1G93A) ALS model mice, and elucidated the underlying mechanisms. HSOD1G93A mice were administered DLT (20 mg·kg-1·d-1, i.g.) from the age of 8 weeks for 10 weeks or until death. ALS onset time and lifespan were determined using rotarod and righting reflex tests, respectively. We found that astrocyte activation accompanying with serotonin receptor 2 A (5HTR2A) upregulation in the spinal cord was tightly associated with ALS-like pathology, which was effectively attenuated by DLT administration. We showed that DLT administration significantly delayed ALS symptom onset time, prolonged lifespan and ameliorated movement disorders, gastrocnemius injury and spinal motor neuronal loss in hSOD1G93A mice. Spinal cord-specific knockdown of 5HTR2A by intrathecal injection of adeno-associated virus9 (AAV9)-si-5Htr2a also ameliorated ALS pathology in hSOD1G93A mice, and occluded the therapeutic effects of DLT administration. Furthermore, we demonstrated that DLT administration promoted autophagy to reduce mutant hSOD1 levels through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocyte neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice. In summary, 5HTR2A antagonism shows promise as a therapeutic strategy for ALS, highlighting the potential of DLT in the treatment of the disease. DLT as a 5HTR2A antagonist effectively promoted autophagy to reduce mutant hSOD1 level through 5HTR2A/cAMP/AMPK pathway, suppressed oxidative stress through 5HTR2A/cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocytic neuroinflammation through 5HTR2A/cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1G93A mice.

Asymmetric catalytic synthesis of chiral covalent organic framework composite (S)-DTP-COF@SiO2 for HPLC enantioseparations by normal-phase and reversed-phase chromatographic modes.

A novel CCOF core-shell composite material (S)-DTP-COF@SiO2 was prepared via asymmetric catalytic and in situ growth strategy. The prepared (S)-DTP-COF@SiO2 was utilized as separation medium for HPLC enantioseparation using normal-phase and reversed-phase chromatographic modes, which displays excellent chiral separation performance for alcohols, esters, ketones, and epoxides, etc. Compared with chiral commercial chromatographic columns (Chiralpak AD-H and Chiralcel OD-H columns) and some previously reported chiral CCOF@SiO2 (CC-MP CCTF@SiO2 and MDI-ß-CD-modified COF@SiO2)-packed columns, there are 4, 3, 13, and 15 tested racemic compounds that could not be resolved on the Chiralpak AD-H column, Chiralcel OD-H column, CC-MP CCTF@SiO2 column, and MDI-ß-CD-modified COF@SiO2 column, respectively, which indicates that the resolution effect of (S)-DTP-COF@SiO2-packed column can be complementary to the other ones. The effects of the analyte mass, column temperature, and mobile phase composition on the enantiomeric separation were investigated. The chiral column exhibits good reproducibility after multiple consecutive injections. The RSDs (n = 5) of the peak area and retention time were less than 1.5% for repetitive separation of 2-methoxy-2-phenylethanol and 1-phenyl-1-pentanol. The chiral core-shell composite (S)-DTP-COF@SiO2 exhibited good enantiomeric separation performance, which not only demonstrates its potential as a novel CSP material in HPLC but also expands the range of applications for chiral COFs.

A nomogram for predicting post-operative hydrocephalus in children with medulloblastoma.

Post-operative hydrocephalus is common among children with medulloblastoma after initial tumor resection. This study aimed to establish a novel model for predicting the development of post-operative hydrocephalus in children with medulloblastoma. Only pediatric patients who received initial medulloblastoma resection at Beijing Tiantan Hospital between January 2018 and May 2021 were included in this study. The potential risk factors associated with post-operative hydrocephalus were identified based on multivariate logistic regression and the nomogram. Receiver operating characteristic (ROC) curve were used to evaluate the performance of the nomogram model based on an independent cohort of medulloblastoma patients who underwent surgery from June 2021 to March 2022. A total of 105 patients were included in the primary cohort. Superior invasion (P = 0.007), caudal invasion (P = 0.025), and intraventricular blood ≥ 5 mm (P = 0.045) were significantly related to the development of post-operative hydrocephalus and thus were assembled into the nomogram model. The model accurately predicted post-operative hydrocephalus based on the calibration curve. The area under the ROC curves for the primary and validation cohorts was 0.849 and 0.855, respectively. In total, the nomogram we developed may aid clinicians in assessing the potential risk of pediatric patients with MB developing post-operative hydrocephalus, especially those who would otherwise not have received a diversionary procedure at presentation.

ISRIB inhibits the senescence of type II pulmonary epithelial cells to alleviate pulmonary fibrosis induced by silica in mice.

The role and mechanisms of integrated stress response inhibitor (ISRIB) on silicosis are still not well defined. In the present study, the effects of ISRIB on cellular senescence and pulmonary fibrosis in silicosis were evaluated by RNA sequencing, micro-computed tomography, pulmonary function assessment, histological examination, and Western blot analysis. The results showed that ISRIB significantly reduced the degree of pulmonary fibrosis in mice with silicosis and reduced the expression of type I collagen, fibronectin, α-smooth muscle actin, and transforming growth factor-ß1. Both in vivo and in vitro results showed that ISRIB reversed the expression of senescence-related factors ß-galactosidase, phosphor-ataxia telangiectasia mutated, phosphor-ataxia telangiectasia and Rad3-related protein, p-p53, p21, p16, and plasminogen activator inhibitor type 1. The aforementioned results were consistent with the sequencing results. These findings implied that ISRIB might reduce the degree of pulmonary fibrosis in mice with silicosis by inhibiting the cellular senescence of alveolar epithelial cell type II.

Radiomics signature for the prediction of progression-free survival and radiotherapeutic benefits in pediatric medulloblastoma.

PURPOSE: To develop and validate a radiomics signature for progression-free survival (PFS) and radiotherapeutic benefits in pediatric medulloblastoma. MATERIALS AND METHODS: We retrospectively enrolled 253 consecutive children with medulloblastoma from two hospitals. A total of 1294 radiomic features were extracted from the region of tumor on the T1-weighted and contrast-enhanced T1-weighted (CE-T1w) MRI. Radiomic feature selection and machine learning modelling were performed to build radiomics signature for the prediction of PFS on the training set. Moreover, the prognostic performance of the clinical parameters was investigated for PFS. The Concordance index (a value of 0.5 indicates no predictive discrimination, and a value of 1 indicates perfect predictive discrimination) was used to measure and compare the prognostic performance of these models. RESULTS: The radiomics signature for the prediction of the PFS yielded Concordance indices of 0.711, 0.707, and 0.717 on the training and held-out test sets 1 and 2, respectively. The radiomics nomogram integrating the radiomics signature, age, and metastasis performed better than the nomogram incorporating only clinicopathological factors (C-index, 0.723 vs. 0.665 and 0.722 vs. 0.677 on the held-out test sets 1 and 2, respectively), which was also validated by the good calibration and decision curve analysis. Further analysis demonstrated that patients with lower value of radiomics signature were associated with better clinical outcomes after postoperative radiotherapy (p < 0.001). CONCLUSION: The radiomics signature and nomogram performed well for the prediction of PFS and could stratify patients underwent postoperative radiotherapy into the high- and low-risk groups with significantly different clinical outcomes.

The role of imaging features and resection status in the survival outcome of sporadic optic pathway glioma children receiving different adjuvant treatments.

Optic pathway glioma (OPG) is a rare brain tumor affecting children, with no standard treatment strategy. This study described the sporadic OPG survival outcomes after surgical treatment and analyzed the role of imaging features and resection status in children receiving different adjuvant treatments. This retrospective study included 165 OPG patients whose clinical information were obtained from the hospital record system. Tumor volume and residual tumor volume were calculated by delineating the lesion area. Kaplan-Meier method and Cox proportional hazards model were conducted to analyze the independent prognosis factor. A total of 165 patients were included in this study. Respectively, the 5-year overall survival (OS) and progression-free survival (PFS) were 87.58% and 77.87%. Residual tumor size and first adjuvant treatment (AT) after surgery were both associated with PFS. In patients with small-size residual tumors, there was no significant difference in PFS between the AT treatment groups. Moreover, age, exophytic cystic components, leptomeningeal metastases, and AT were associated with OS. In patients with exophytic cystic components and those with leptomeningeal metastases, there was no significant difference in OS. Our results revealed that OPG patients could avoid or defer AT by maximized resection. Age ≤ 2 years was a disadvantageous factor for OS. Patients with exophytic cystic components were more likely to benefit from primary surgery, and CT or RT was not beneficial for these patients. Patients with leptomeningeal metastases had a poor prognosis regardless of the treatment they received. Future prospective clinical studies are needed to develop more effective treatment regimens.

SARM1 deletion restrains NAFLD induced by high fat diet (HFD) through reducing inflammation, oxidative stress and lipid accumulation.

SARM1 (Sterile alpha and armadillo motif-containing protein 1) is the recently identified TIR domain-containing cytosolic protein, which is involved in toll-like receptors (TLRs) signaling transduction. In the present study, the role of SARM1 in high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) progression was explored. We found that SARM1 was expressed highly in fatty liver. And SARM1-knockout (KO) reduced steatohepatitis and metabolic disorders induced by HFD. SARM1-deletion decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in HFD-fed mice. Additionally, inflammatory response caused by HFD was alleviated by SARM1-deletion through inactivating TLR4/7/9 and nuclear factor kappa B (NF-κB) pathways. Of note, SARM1-deletion also reduced the expressions of inflammation-associated molecules in hypothalamus of HFD-fed mice. Furthermore, HFD administration led to oxidative stress in liver of mice, while being decreased in SARM1-KO mice. Moreover, SARM1-ablation improved lipid dyslipidemia by suppressing the mRNA levels of genes, linked to glycolysis, lipogenesis and transcriptional regulation. Insulin resistance was also attenuated by SARM1-deficiency through enhancing the activation of liver Akt/glycogen synthase kinase-3ß (GSK3ß) and insulin receptor substrate-1 (IRS1)/FOXO1 pathways in HFD-fed mice. Also, SARM1-knockout improved neuropeptide Y (NPY), Pro-Opiomelanocortins (POMC), Agouti-related Protein (AGRP) and Cocaine-and-Amphetamine Responsive Transcript 1 (CART1) expressions in hypothalamus of mice after HFD administration. In vitro, we found that the reduction of inflammatory response, oxidative stress and dyslipidemia induced by SARM1-knockout in primary hepatocytes after fructose stimulation was largely attributed to its suppression to TLR4/7/9. Together, the findings demonstrated that SARM1 might be an effective target for developing effective therapeutic strategies against NAFLD.

Differential analysis of clinical efficacy on patients with serious infection in ICU by different meropenem regimens.

To investigate the difference in clinical efficacy and safety of different meropenem regimens on patients with serious infection in ICU. Then, 228 patients with serious infection in ICU were divided by random into control group (intermittent administration in 1000mg/30min single dose) and research group (continuous administration in 200mg/10min +800mg/180min), respectively. The blood concentration of meropenem were recorded in two groups at different time points, and difference in treatment effectiveness, iconographic effectiveness, bacterial eradication rate, 28-day survival rate and many other clinical scoring indices (SOFA, APACHEII, CPIS, and SIRS) were compared between two groups. There were 212 patients completing the whole research, including 104 patients in research group and 108 patients in control group. The difference in treatment effectiveness (77.8% vs 53.7%), iconographic effectiveness (51.0% vs 18.5%), and 28-day survival rate (86.5% vs 64.8%) between two groups performed statistical significance (P<0.05). However, the difference in bacterial eradication rate (48.0% vs 46.3%) performed no statistical significance. Eight hours later, the difference in average blood concentration between two groups (9.61±3.63µg/ml vs 1.5±0.51µg/ml) showed statistical significance. Moreover, the difference in clinical scoring indices except APACHE II score between two groups performed statistical significance. It was helpful to maintain the blood concentration of meropenem by extending the transfusion time. Therefore, it could increase the clinical cure rate and 28-day survival of patients with serious infection in ICU, improve clinical indices, and reduce the usage amount of antibiotics.

Breaking cover: neural responses to slow and fast camouflage-breaking motion.

Primates need to detect and recognize camouflaged animals in natural environments. Camouflage-breaking movements are often the only visual cue available to accomplish this. Specifically, sudden movements are often detected before full recognition of the camouflaged animal is made, suggesting that initial processing of motion precedes the recognition of motion-defined contours or shapes. What are the neuronal mechanisms underlying this initial processing of camouflaged motion in the primate visual brain? We investigated this question using intrinsic-signal optical imaging of macaque V1, V2 and V4, along with computer simulations of the neural population responses. We found that camouflaged motion at low speed was processed as a direction signal by both direction- and orientation-selective neurons, whereas at high-speed camouflaged motion was encoded as a motion-streak signal primarily by orientation-selective neurons. No population responses were found to be invariant to the camouflage contours. These results suggest that the initial processing of camouflaged motion at low and high speeds is encoded as direction and motion-streak signals in primate early visual cortices. These processes are consistent with a spatio-temporal filter mechanism that provides for fast processing of motion signals, prior to full recognition of camouflage-breaking animals.

Autophagy and hippocampal neuronal injury.

BACKGROUND: Autophagy is a specific universal biological phenomenon in eukaryotic cells, which is characterized by cytoplasmic vacuoles in the process of degrading cellular contents in lysosomes. The hippocampus plays an important role in higher nervous activities such as emotional integration, cognition, and memory. As an area closely related to learning and memory functions of the brain, the hippocampus is particularly sensitive to injuries caused by various reasons. PURPOSE: Autophagy has certain links with a variety of causes of hippocampal neuronal injury. This short review discusses and summarizes this correlation with a focus on the possible role of autophagy and mechanisms in it. CONCLUSION: The current correlation between autophagy and hippocampal neuronal injury has not been completely determined by the general public alike. Further studies are needed to determine special effects of autophagy on hippocampal neuronal injury, which might accelerate the development of therapeutic interventions in hippocampal neuronal injury in many neurological disorders.

Misdiagnosis of eosinophilic cystitis: A case report and literature review.

RATIONALE: Eosinophilic cystitis (EC) is a rare and specific transmural inflammatory disease in clinic. At present, its etiology is unknown, its clinical manifestations are diverse, and its auxiliary examination lacks specificity, so it is easy to be missed or misdiagnosed in clinical practice. PATIENT CONCERNS: A 72-year-old male patient with symptoms of lower urinary tract obstruction accompanied by hematuria was diagnosed with benign prostatic hyperplasia with bleeding by B-ultrasound and urinary CT examination. After being treated with catheterization, anti-infection and hemostasis, he was selectively treated with transurethral resection of prostate, but he saw a pattern mass on the right back wall of the bladder during the operation. Considering bladder tumor, he removed the lesion and gave pirarubicin for bladder perfusion. However, the postoperative pathological result was EC. DIAGNOSIS: The diagnosis of EC can only rely on pathological examination, and the accurate and positive rate of biopsy can be improved by obtaining muscle tissue as much as possible at the same time of multi-point biopsy. INTERVENTION: Prednisone and cetirizine were given orally after transurethral resection of lesions, and tamsulosin and finasteride were given regularly to treat benign prostatic hyperplasia. OUTCOMES: No recurrence and abnormal urination were found during the follow-up for half a year, and the upper urinary tract function was normal. LESSONS: The clinical manifestations of EC are atypical, the laboratory examination and imaging examination are not specific, and it is difficult to make a definite diagnosis before operation. The diagnosis depends on pathological examination. Transurethral resection of the lesion can obviously improve the positive rate of biopsy while completely removing the lesion, and the combined drug treatment can achieve satisfactory results in a short period of time. Active follow-up after operation is very important to identify the recurrence of the disease and prevent the upper urinary tract function from being damaged.

Subcomponent self-assembly construction of tetrahedral cage FeII4L4 for high-resolution gas chromatographic separation.

Metal organic cages (MOCs), as an emerging discrete supramolecular compounds, have received widespread attention in separation, biomedicine, gas capture, catalysis, and molecular recognition due to their porosity, adjustability and stability. Herein, we present a new chiral MOC FeII4L4 coated capillary column prepared for gas chromatographic (GC) separation of different types of organic compounds, including n-alkanes, n-alcohols, alkylbenzenes, isomers, especially for racemic compounds. There are 20 different kinds of racemates (e.g., alcohols, ethers, epoxides, esters, alkenes, and aldehydes) were well resolved on the FeII4L4 chiral column and a maximum resolution value for 1-phenyl-1-propanol reaches 6.17. The FeII4L4 coated column exhibited high column efficiency (3100 plates m-1 for n-dodecane) and good enantiomeric resolution complementary to that of a commercial ß-DEX 120 column and the previously reported chiral MOC [Fe4L6] (ClO4)8 coated column. The relative standard deviation (RSDs) of the peak area and retention time of glycidol and nitrotoluene were below 1.2 %. This study reveals that chiral MOCs have good application prospects in chromatographic separation.

Distinct functional organizations for processing different motion signals in V1, V2, and V4 of macaque.

Motion perception is qualitatively invariant across different objects and forms, namely, the same motion information can be conveyed by many different physical carriers, and it requires the processing of motion signals consisting of direction, speed, and axis or trajectory of motion defined by a moving object. Compared with the representation of orientation, the cortical processing of these different motion signals within the early ventral visual pathway of the primate remains poorly understood. Using drifting full-field noise stimuli and intrinsic optical imaging, along with cytochrome-oxidase staining, we found that the orientation domains in macaque V1, V2, and V4 that processed orientation signals also served to process motion signals associated with the axis and speed of motion. In contrast, direction domains within the thick stripes of V2 demonstrated preferences that were independent of motion speed. The population responses encoding the orientation and motion axis could be precisely reproduced by a spatiotemporal energy model. Thus, our observation of orientation domains with dual functions in V1, V2, and V4 directly support the notion that the linear representation of the temporal series of retinotopic activations may serve as another motion processing strategy in primate ventral visual pathway, contributing directly to fine form and motion analysis. Our findings further reveal that different types of motion information are differentially processed in parallel and segregated compartments within primate early visual cortices, before these motion features are fully combined in high-tier visual areas.

Equivalent representation of real and illusory contours in macaque V4.

The cortical processing of illusory contours provides a unique window for exploring the brain mechanisms underlying visual perception. Previous electrophysiological single-cell recordings demonstrate that a subgroup of cells in macaque V1 and V2 signal the presence of illusory contours, whereas recent human brain imaging studies reveal higher-order visual cortices playing a central role in illusory figure processing. It seems that the processing of illusory contours/figures may engage multiple cortical interactions between hierarchically organized processing stages in the ventral visual pathway of primates. However, it is not yet known in which brain areas illusory contours are represented in the same manner as real contours at both the population and single-cell levels. Here, by combining intrinsic optical imaging in anesthetized rhesus macaques with single-cell recordings in awake ones, we found a complete overlap of orientation domains in visual cortical area V4 for processing real and illusory contours. In contrast, the orientation domains mapped in early visual areas V1 and V2 mainly encoded the local physical stimulus features inducing the subjective perception of global illusory contours. Our results indicate that real and illusory contours are encoded equivalently by the same functional domains in V4, suggesting that V4 is a key cortical locus for integration of local features into global contours.

Effects of repetitive transcranial magnetic stimulation on post-stroke patients with cognitive impairment: A systematic review and meta-analysis.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is one of the common symptoms in stroke survivors, by which their quality of life and rehabilitation progress are severely limited. Repetitive transcranial magnetic stimulation (rTMS) has been proven to regulate cognition in a non-invasive way. However, the inconsistency in its effectiveness on PSCI reported in previous studies cannot be ruled out. A critical and comprehensive systematic review of rTMS on PSCI patients is necessary. METHODS: Trials published before the end of February 2022 on rTMS and PSCI were systematically retrieved from PubMed, Cochrane Library, EBSCO, Embase and SCOPUS. High-quality literature was selected following the inclusion and exclusion criteria, with their references being screened. Meta-analysis of data was carried out using RevMan 5.4 software. RESULTS: Ten trials involving 347 participants were included in the current review. Global cognition as measured by MMSE or MoCA (SMD=0.54; 95% CI=0.31, 0.76; P < 0.00001; I2 = 38%) and modified Barthel index (MD=9.00; 95% CI=2.93, 15.06; P = 0.004; I2 = 0%) were significantly improved by rTMS compared to sham stimulation in PSCI patients. Performance of the digit symbol test, rivermead behavioral memory test and attention in PSCI patients were also significantly improved. Subgroup analyses showed that significant differences were found in both MoCA and MMSE among PSCI patients by rTMS. MoCA was significantly improved by high frequency rTMS, while both MoCA and MMSE were significantly improved targeting on left dorsolateral prefrontal cortex. CONCLUSION: rTMS provides a non-invasive and effective technique for the treatment of post-stroke patients with cognitive impairment.

Long-range connectome of pyramidal neurons in the sensorimotor cortex.

The neocortex mediates information processing through highly organized circuitry that contains various neuron types. Distinct populations of projection neurons in different cortical regions and layers make specific connections and participate in distinct physiological functions. Herein, with the fluorescence micro-optical sectioning tomography (fMOST) and transgenetic mice that targeted intratelencephalic (IT) and pyramidal tract (PT) neurons at specific layers, we dissected the long-range connectome of pyramidal neurons in six subregions of the sensorimtor cortex. The distribution of the input neurons indicated that IT and PT neurons in the same region received information from similar regions, while the neurons in different subregions received from the preferred neuron populations. Both the input and projection areas of these six subregions showed the transverse and longitudinal correspondence in the cortico-cortical, cortico-thalamic, and cortico-striatal circuits, which indicated that the connections were topologically organized. This study provides a comprehensive resource on the anatomical connections of cortical circuits.

Cortical glutamatergic projection neuron types contribute to distinct functional subnetworks.

The cellular basis of cerebral cortex functional architecture remains not well understood. A major challenge is to monitor and decipher neural network dynamics across broad cortical areas yet with projection-neuron-type resolution in real time during behavior. Combining genetic targeting and wide-field imaging, we monitored activity dynamics of subcortical-projecting (PTFezf2) and intratelencephalic-projecting (ITPlxnD1) types across dorsal cortex of mice during different brain states and behaviors. ITPlxnD1 and PTFezf2 neurons showed distinct activation patterns during wakeful resting, during spontaneous movements and upon sensory stimulation. Distinct ITPlxnD1 and PTFezf2 subnetworks were dynamically tuned to different sensorimotor components of a naturalistic feeding behavior, and optogenetic inhibition of ITsPlxnD1 and PTsFezf2 in subnetwork nodes disrupted distinct components of this behavior. Lastly, ITPlxnD1 and PTFezf2 projection patterns are consistent with their subnetwork activation patterns. Our results show that, in addition to the concept of columnar organization, dynamic areal and projection-neuron-type specific subnetworks are a key feature of cortical functional architecture linking microcircuit components with global brain networks.