Search

Background: The ventral tegmental area (VTA) contains heterogeneous cell populations. The dopaminergic neurons in VTA play a central role in reward and cognition, while CamKIIα-positive neurons, composed mainly of glutamatergic and some dopaminergic neurons, participate in the reward learning and locomotor activity behaviors. The differences in brain-wide functional and structural networks between these two neuronal subtypes were comparatively elucidated., Methods: In this study, we applied a method combining Designer Receptors Exclusively Activated by Designer Drugs (DREADD) and fMRI to assess the cell type-specific modulation of whole-brain neural networks. rAAV encoding the cre-dependent hM3D was injected into the right VTA of DAT-cre or CamKIIα-cre transgenic rats. The global brain activities elicited by DREADD stimulation were then detected using BOLD-fMRI. Furthermore, the cre-dependent antegrade transsynaptic viral tracer H129ΔTK-TT was applied to label the outputs of VTA neurons., Results: We found that DREADD stimulation of dopaminergic neurons induced significant BOLD signal changes in the VTA and several VTA-related regions including mPFC, Cg and Septum. More regions responded to selective activation of VTA CamKIIα-positive neurons, resulting in increased BOLD signals in VTA, Insula, mPFC, MC_R (Right), Cg, Septum, Hipp, TH_R, PtA_R, and ViC_R. Along with DREADD-BOLD analysis, further neuronal tracing identified multiple cortical (MC, mPFC) and subcortical (Hipp, TH) brain regions that are structurally and functionally connected by VTA dopaminergic and CamKIIα-positive neurons., Conclusions: Our study dissects brain-wide structural and functional networks of two neuronal subtypes in VTA and advances our understanding of VTA functions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The investigation of neural circuits is important for interpreting both healthy brain function and psychiatric disorders. Currently, the architecture of neural circuits is always investigated with fluorescent protein encoding neurotropic virus and ex vivo fluorescent imaging technology. However, it is difficult to obtain a whole-brain neural circuit connection in living animals, due to the limited fluorescent imaging depth. Herein, the noninvasive, whole-brain imaging technique of MRI and the hypotoxicity virus vector AAV (adeno-associated virus) were combined to investigate the whole-brain neural circuits in vivo. AAV2-retro are an artificially-evolved virus vector that permits access to the terminal of neurons and retrograde transport to their cell bodies. By expressing the ferritin protein which could accumulate iron ions and influence the MRI contrast, the neurotropic virus can cause MRI signal changes in the infected regions. For mice injected with the ferritin-encoding virus vector (rAAV2-retro-CAG-Ferritin) in the caudate putamen (CPu), several regions showed significant changes in MRI contrasts, such as PFC (prefrontal cortex), HIP (hippocampus), Ins (insular cortex) and BLA (basolateral amygdala). The expression of ferritin in those regions was also verified with ex vivo fluorescence imaging. In addition, we demonstrated that changes in T2 relaxation time could be used to identify the spread area of the virus in the brain over time. Thus, the neural connections could be longitudinally detected with the in vivo MRI method. This novel technique could be utilized to observe the viral infection process and detect the neural circuits in a living animal., (© 2021 Innovation Academy for Precision Measurement Science and Technology. Human Brain Mapping published by Wiley Periodicals LLC.)

The elucidation of neural networks is essential to understanding the mechanisms of brain functions and brain disorders. Neurotropic virus-based trans-synaptic tracing tools have become an effective method for dissecting the structure and analyzing the function of neural-circuitry. However, these tracing systems rely on fluorescent signals, making it hard to visualize the panorama of the labeled networks in mammalian brain in vivo. One MRI method, Diffusion Tensor Imaging (DTI), is capable of imaging the networks of the whole brain in live animals but without information of anatomical connections through synapses. In this report, a chimeric gene coding for ferritin and enhanced green fluorescent protein (EGFP) was integrated into Vesicular stomatitis virus (VSV), a neurotropic virus that is able to spread anterogradely in synaptically connected networks. After the animal was injected with the recombinant VSV (rVSV), rVSV-Ferritin-EGFP, into the somatosensory cortex (SC) for four days, the labeled neural-network was visualized in the postmortem whole brain with a T2-weighted MRI sequence. The modified virus transmitted from SC to synaptically connected downstream regions. The results demonstrate that rVSV-Ferritin-EGFP could be used as a bimodal imaging vector for detecting synaptically connected neural-network with both ex vivo MRI and fluorescent imaging. The strategy in the current study has the potential to longitudinally monitor the global structure of a given neural-network in living animals., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Owing to advancements in non-invasive magnetic resonance imaging, many studies have repeatedly showed that diabetes affects the central nervous system in the presence of peripheral neuropathy, suggesting a common or interacting pathological mechanism for both complications. Methods: We aimed to investigate the role of abnormal gut microbiota in rats with diabetic peripheral neuropathy (DPN) combined with cognitive dysfunction. Glucose-compliant rats with nerve conduction deficits were screened as a successful group of DPN rats. The DPN group was then divided into rats with combined cognitive impairment (CD) and rats with normal cognitive function (NCD) based on the results of the Novel object recognition test. Rat feces were then collected for 16S rRNA gene sequencing of the intestinal flora. Results and Discussion: The results revealed that abnormalities in Firmicutes, Ruminococcaceae, Bacteroidia, and Actinobacteria-like microorganisms may induce DPN complicated by cognitive dysfunction. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused several outbreaks of highly contagious respiratory diseases worldwide. The respiratory symptoms of Coronavirus Disease-19 (COVID-19) have been closely monitored and studied, while the central nervous system (CNS) and peripheral system (PNS) lesions induced by COVID-19 have not received much attention. Currently, patients with COVID-19-associated encephalopathy present with dizziness, headache, anxiety and depression, stroke, epileptic seizures, the Guillain-Barre syndrome (GBS), and demyelinating disease. The exact pathologic basis for these neurological symptoms is currently not known. Rapid mutation of the SARS-CoV-2 genome leads to the appearance of SARS-CoV-2 variants of concern (VOCs), which have higher infectivity and virulence. Therefore, this narrative review will focus on the imaging assessment of COVID-19 and its VOC. There has been an increase in technologies, such as [18F]fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and functional magnetic resonance imaging (fMRI), that have been used to observe changes in brain microstructure over time in patients with COVID-19 recovery. Medical imaging and pathological approaches aimed at exploring the associations between COVID-19 and its VOC, with cranial nerve and abnormal nerve discharge will shed light on the rehabilitation process of brain microstructural changes related to SARS-CoV-2, and aid future research in our understanding of the treatment and prognosis of COVID-19 encephalopathy. [ABSTRACT FROM AUTHOR]

Propofol is the most common intravenous anesthetic agent for induction and maintenance of anesthesia, and has been used clinically for more than 30 years. However, the mechanism by which propofol induces loss of consciousness (LOC) remains largely unknown. The adenosine A2A receptor (A2AR) has been extensively proven to have an effect on physiological sleep. It is, therefore, important to investigate the role of A2AR in the induction of LOC using propofol. In the present study, the administration of the highly selective A2AR agonist (CGS21680) and antagonist (SCH58261) was utilized to investigate the function of A2AR under general anesthesia induced by propofol by means of animal behavior studies, resting‐state magnetic resonance imaging and c‐Fos immunofluorescence staining approaches. Our results show that CGS21680 significantly prolonged the duration of LOC induced by propofol, increased the c‐Fos expression in nucleus accumbens (NAc) and suppressed the functional connectivity of NAc‐dorsal raphe nucleus (DR) and NAc‐cingulate cortex (CG). However, SCH58261 significantly shortened the duration of LOC induced by propofol, decreased the c‐Fos expression in NAc, increased the c‐Fos expression in DR, and elevated the functional connectivity of NAc‐DR and NAc‐CG. Collectively, our findings demonstrate the important roles played by A2AR in the LOC induced by propofol and suggest that the neural circuit between NAc‐DR maybe controlled by A2AR in the mechanism of anesthesia induced by propofol. [ABSTRACT FROM AUTHOR]

A mammalian brain contains numerous neurons with distinct cell types for complex neural circuits. Virus-based circuit tracing tools are powerful in tracking the interaction among the different brain regions. However, detecting brain-wide neural networks in vivo remains challenging since most viral tracing systems rely on postmortem optical imaging. We developed a novel approach that enables in vivo detection of brain-wide neural connections based on metal-free magnetic resonance imaging (MRI). The recombinant adeno-associated virus (rAAV) with retrograde ability, the rAAV2-retro, encoding the human water channel aquaporin 1 (AQP1) MRI reporter gene was generated to label neural connections. The mouse was micro-injected with the virus at the Caudate Putamen (CPU) region and subjected to detection with Diffusion-weighted MRI (DWI). The prominent structure of the CPU-connected network was clearly defined. In combination with a Cre-loxP system, rAAV2-retro expressing Cre-dependent AQP1 provides a CPU-connected network of specific type neurons. Here, we established a sensitive, metal-free MRI-based strategy for in vivo detection of cell type-specific neural connections in the whole brain, which could visualize the dynamic changes of neural networks in rodents and potentially in non-human primates. [ABSTRACT FROM AUTHOR]