A whole-brain male mouse atlas of long-range inputs to histaminergic neurons.

The precise structural and functional characteristics of input circuits targeting histaminergic neurons remain poorly understood. Here, using a rabies virus retrograde tracing system combined with fluorescence micro-optical sectioning tomography, we construct a 3D monosynaptic long-range input atlas of male mouse histaminergic neurons. We identify that the hypothalamus, thalamus, pallidum, and hippocampus constitute major input sources, exhibiting diverse spatial distribution patterns and neuronal type ratios.

Light-Triggered Graphene/Black Phosphorus Heterostructure FET Platform for Ultrasensitive Detection of Alzheimer's Disease Biomarkers at the Zeptomole Level.

Due to the low concentration of amyloid-beta (Aβ) in plasma and the high content of interfering factors, the conventional detection method for the quantification of Aβ still faces the problem of insufficient limit of detection (LOD). In this work, we propose a new light-triggered graphene-black phosphorus heterostructure (G-BP) field-effect transistor (FET) biosensing platform that achieves a ​​marked​​ reduction in the LOD. The LOD for Alzheimer's disease (AD) biomarker Aβ detection using the G-BP FET is as low as 235.

Ame-miR-2161 affects the survival and development of honeybee larvae through the juvenile hormone acid methyltransferase gene.

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play crucial regulatory roles in insect growth and development. However, the coordinated regulation of honeybee development by miRNAs and hormones remains poorly understood. In this study, the regulatory network of target genes for Apis mellifera miRNA-2161 (ame-miR-2161) was constructed, and its association with the survival and development of worker larvae was investigated.

Integrated Classification of Cortical Cells and Quantitative Projectomic Mapping Unveil Organizational Principles of Brain-Wide Connectomes at Single Cell Level.

Molecularly defined cortical cell types have recently been linked to whole neuronal morphology (WNM), particularly those characterized by whole-brain-wide projections, such as intratelencephalic (IT), extratelencephalic (ET), and corticothalamic (CT) neurons. In contrast, classical morphological classifications (e.g.

Single-neuron projectomes of macaque prefrontal cortex reveal refined axon targeting and arborization.

Cortical expansion endows advanced cognitive functions in primates, and whole-brain single-neuron projection analysis helps to elucidate underlying neural circuit mechanisms. Here, we reconstructed 2,231 single-neuron projectomes for the macaque prefrontal cortex (PFC) and identified 32 projectome-based subtypes of intra-telencephalic, pyramidal-tract, and cortico-thalamic neurons. Each subtype exhibited distinct topography in their soma distribution within the PFC, a characteristic pattern of axon targeting, and subregion-specific patchy terminal arborization in the targeted area, with putative functions annotated.

Mesoscopic mapping of the brain: From rodents to primates.

Advances in brain mapping technologies have made substantial progress in identifying diverse cell types and their connectivity. Focusing on papers recently contributed by the Mesoscopic Brain Mapping Consortium to Cell, Neuron, and Developmental Cell, this commentary discusses insights into brain organization, development, evolution, and diseases, as well as future research directions.

A mouse brain stereotaxic topographic atlas with isotropic 1-μm resolution.

Multi-omics studies, represented by connectomes and spatial transcriptomes, have entered the era of single-cell resolution, necessitating a reference brain atlas with spatial localization capability at the single-cell level. However, such atlases are unavailable. Here we present a whole mouse brain dataset of Nissl-based cytoarchitecture with isotropic 1-μm resolution, achieved through continuous micro-optical sectioning tomography.

Quantitative longitudinal investigation of non-alcoholic steatohepatitis in mice by photoacoustic microscopy.

Non-alcoholic steatohepatitis (NASH) is a prevalent chronic liver disease characterized by significant alterations in liver microvascular structures, leading to microcirculatory dysfunction and potentially contributing to various extrahepatic complications. In this study, we propose a longitudinal investigative pipeline based on liver photoacoustic microscopy (LPAM), integrating optical-resolution photoacoustic microscopy (OR-PAM), a modular liver window (MLW), a custom 3D-printed liver imaging mount (LIM), and a dedicated vessel-sinusoid separation and analysis method. This pipeline enabled continuous monitoring and quantitative assessment of microvascular changes in a NASH mouse model over a six-week period.

A dorsal subiculum-medial mammillary body pathway for spatial memory.

The dorsal subiculum (dSub) and medial mammillary body (MM) are essential components of the extended hippocampal system, heavily implicated in spatial memory processes. However, the exact function of the prominent dSub-to-MM projection has remained ambiguous. Here, integrating c-fos mapping, fiber photometry, optogenetic manipulations and behavioral paradigms, we found that the monosynaptic connection between dSub and MM, rather than collaterals to other regions, is not only involved in spatial memory retrieval but also highly vulnerable to perturbations on activity level in both directions.

Neuroprotective liver portal area macrophages attenuate hepatic inflammation.

Tissue macrophages have an important role in the maintenance of liver homeostasis, and their functions are closely related to spatial localization. Here, through integration of whole liver lobe imaging and single-cell RNA sequencing analysis of CX3CR1 cells in the mouse liver, we identified a dense network of CX3CR1CD63 liver portal area macrophages (LPAMs) that exhibited transcriptional and spatial differences compared with CX3CR1CD207 liver capsular macrophages. The survival of LPAMs was dependent on colony-stimulating factor 1 receptor (CSF1R).

Label-free whole-kidney metabolic optical imaging using insulated cryofixation and cryo-micro-optical sectioning tomography.

Cryo-imaging has the potential to obtain and visualize the metabolic state of the whole kidney without labeling. However, uneven fixation of metabolic information and incomplete organ morphology in three dimensions limit cryo-imaging application. Here, a pipeline of insulated cryofixation combined with cryo-micro optical sectioning tomography (cryo-MOST) was established to achieve uniform and complete cryofixation and three-dimensional visualization of renal metabolic mapping at a micron-scale resolution.

The crosstalk of monocyte-neutrophil in hair follicles regulates neutrophil transepidermal migration in contact dermatitis.

The excessive accumulation of neutrophils within the epidermis is a significant hallmark of cutaneous diseases; however, the mechanisms governing neutrophil transepidermal migration (NTEM) remain inadequately understood. In this study, we develop trichromatic-fluorescence-labeled chimeric mice by utilizing Cx3cr1Lyz2 mice as bone marrow donors and Krt14 mice as recipients. This approach enables us to visualize the process of NTEM and the crosstalk between neutrophils and monocytes in a murine model of irritant contact dermatitis (ICD).

Analysis of the Expression Patterns of piRNAs in Response to Microsporidian Invasion in Midgut of Workers ().

Piwi-interacting RNAs (piRNAs) play an essential part in transposon suppression, DNA methylation, and antiviral responses. The current understanding of the roles of piRNAs in honeybees is very limited. This study aims to analyze the expression pattern and regulatory role of piRNAs in the Asian honeybee () responding to infection by , based on previously gained small RNA-seq data.

Projectome-based characterization of hypothalamic peptidergic neurons in male mice.

The hypothalamus coordinately regulates physiological homeostasis and innate behaviors, yet the detailed arrangement of hypothalamic axons remains unclear. Here we mapped the whole-brain projections of over 7,000 hypothalamic neurons expressing distinct neuropeptides in male mice, identifying 2 main classes and 31 types using single-neuron projectome analysis. These classes/types exhibited regionally biased soma distribution and specific neuropeptide enrichment.

Single-nucleus transcriptome atlas of the basal forebrain reveals diverse ageing-related pathways.

The basal forebrain is a critical brain region involved in various neurobiological processes, including learning, memory and attention. Basal forebrain cells undergo structural and functional changes during ageing, increasing their vulnerability to neurodegenerative diseases. To reveal the molecular landscape of distinct cell types during development and early ageing, we constructed a comprehensive single-nucleus transcriptomic atlas spanning postnatal Days 4 and 14 and 3, 9 and 15 months of age.

Long-range inputome of prefrontal GABAergic interneurons in the Alzheimer's disease mouse.

Introduction: Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by damage to cortical circuits. However, the mechanisms underlying AD-associated changes in long-range circuits remain poorly understood.

Methods: In this study, we used viral tracing and fluorescence micro-optical sectioning tomography (fMOST) imaging to investigate whole-brain changes in the input circuit of the frontal cortex of 5×FAD mice.

Optical sectioning methods in three-dimensional bioimaging.

In recent advancements in life sciences, optical microscopy has played a crucial role in acquiring high-quality three-dimensional structural and functional information. However, the quality of 3D images is often compromised due to the intense scattering effect in biological tissues, compounded by several issues such as limited spatiotemporal resolution, low signal-to-noise ratio, inadequate depth of penetration, and high phototoxicity. Although various optical sectioning techniques have been developed to address these challenges, each method adheres to distinct imaging principles for specific applications.

Knowledge mining of brain connectivity in massive literature based on transfer learning.

Motivation: Neuroscientists have long endeavored to map brain connectivity, yet the intricate nature of brain networks often leads them to concentrate on specific regions, hindering efforts to unveil a comprehensive connectivity map. Recent advancements in imaging and text mining techniques have enabled the accumulation of a vast body of literature containing valuable insights into brain connectivity, facilitating the extraction of whole-brain connectivity relations from this corpus. However, the diverse representations of brain region names and connectivity relations pose a challenge for conventional machine learning methods and dictionary-based approaches in identifying all instances accurately.

Neuronal diversity and stereotypy at multiple scales through whole brain morphometry.

We conducted a large-scale whole-brain morphometry study by analyzing 3.7 peta-voxels of mouse brain images at the single-cell resolution, producing one of the largest multi-morphometry databases of mammalian brains to date. We registered 204 mouse brains of three major imaging modalities to the Allen Common Coordinate Framework (CCF) atlas, annotated 182,497 neuronal cell bodies, modeled 15,441 dendritic microenvironments, characterized the full morphology of 1876 neurons along with their axonal motifs, and detected 2.

Imaging quality enhancement in photon-counting single-pixel imaging via an ADMM-based deep unfolding network in small animal fluorescence imaging.

Photon-counting single-pixel imaging (SPI) can image under low-light conditions with high-sensitivity detection. However, the imaging quality of these systems will degrade due to the undersampling and intrinsic photon-noise in practical applications. Here, we propose a deep unfolding network based on the Bayesian maximum a posterior (MAP) estimation and alternating direction method of multipliers (ADMM) algorithm.

Supercontinuum-tailoring multicolor imaging reveals spatiotemporal dynamics of heterogeneous tumor evolution.

Tumor heterogeneity and tumor evolution contribute to cancer treatment failure. To understand how selective pressures drive heterogeneous tumor evolution, it would be useful to image multiple important components and tumor subclones in vivo. We propose a supercontinuum-tailoring two-photon microscope (SCT-TPM) and realize simultaneous observation of nine fluorophores with a single light beam, breaking through the 'color barrier' of intravital two-photon fluorescence imaging.

ame-miR-5119- axis modulates larval-pupal transition of western honeybee worker.

The miRNA plays a key role in the regulation of hormone signaling in insects. The pathways by which miRNAs affect hormone levels are unclear in the honeybee (), an indispensable pollinator in nature. In this study, ame-miR-5119 was overexpressed and knocked down in larvae by feeding mimics and inhibitors, respectively, and we determined that ame-miR-5119 regulates hormone signaling through the target gene ecdysis triggering hormone (), which affects the larval-pupal transition of workers.

From Individual to Population: Circuit Organization of Pyramidal Tract and Intratelencephalic Neurons in Mouse Sensorimotor Cortex.

The sensorimotor cortex participates in diverse functions with different reciprocally connected subregions and projection-defined pyramidal neuron types therein, while the fundamental organizational logic of its circuit elements at the single-cell level is still largely unclear. Here, using mouse Cre driver lines and high-resolution whole-brain imaging to selectively trace the axons and dendrites of cortical pyramidal tract (PT) and intratelencephalic (IT) neurons, we reconstructed the complete morphology of 1,023 pyramidal neurons and generated a projectome of 6 subregions within the sensorimotor cortex. Our morphological data revealed substantial hierarchical and layer differences in the axonal innervation patterns of pyramidal neurons.

A hierarchically annotated dataset drives tangled filament recognition in digital neuron reconstruction.

Reconstructing neuronal morphology is vital for classifying neurons and mapping brain connectivity. However, it remains a significant challenge due to its complex structure, dense distribution, and low image contrast. In particular, AI-assisted methods often yield numerous errors that require extensive manual intervention.

Graph-based cell pattern recognition for merging the multi-modal optical microscopic image of neurons.

A deep understanding of neuron structure and function is crucial for elucidating brain mechanisms, diagnosing and treating diseases. Optical microscopy, pivotal in neuroscience, illuminates neuronal shapes, projections, and electrical activities. To explore the projection of specific functional neurons, scientists have been developing optical-based multimodal imaging strategies to simultaneously capture dynamic in vivo signals and static ex vivo structures from the same neuron.