Xuemei Liu

High-density micro-electrocorticography (μECoG) arrays offer precise spatial resolution with minimal invasiveness. This study employed a custom ultra-thin 64-channel μECoG array to investigate cortical activity in mice under chronic caffeine exposure. While caffeine is known to enhance short-term alertness, its long-term impact on sleep microarchitecture and brain connectivity is unclear. Continuous recordings from adult mice during baseline and recovery revealed that prolonged caffeine intake significantly reduced broadband power spectral density (PSD) and spindle power but increased interregional coherence and altered spindle duration and density. In contrast, six hours of sleep deprivation elevated PSD and coherence, mainly affecting sensorimotor and retrosplenial cortices. These findings validate the μECoG array’s functionality and demonstrate that post-chronic caffeine withdrawal lowers cortical oscillatory power yet enhances network connectivity, whereas acute sleep loss boosts global synchrony. This work clarifies how sustained caffeine use and sleep deprivation distinctly disrupt sleep homeostasis through different neural mechanisms.

Midbrain dopamine (DA) neurons are essential for regulating movement, emotion, and reward, with their dysfunction closely linked to Parkinson’s disease (PD). While DA neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) have known overlapping roles in behaviors such as depression and reward, their distinct contributions to subtle spontaneous behaviors remain insufficiently understood. In this study, we utilized a 3D behavioral analysis platform powered by machine learning to explore motor and nuanced behavioral changes in a subacute MPTP mouse model of PD. This investigative approach was combined with cell-type-specific genetic ablation of DA neurons in both the SNc and VTA. Our findings highlight significant deficits in rearing, walking, and hunching behaviors correlated with the loss of SNc DA neurons, but not VTA DA neurons, alongside increased overall movement, reduced movement precision, and pronounced right-sided lateralization. These subtle features, particularly rearing deficits and lateralization, emerge as critical behavioral biomarkers of SNc DA neuron loss, thereby enhancing the translational relevance of PD models.

SUMMARY: Rapid escape against visual threats is critical for survival. Whether it requires a permissive mechanism is unknown. Here, we show that osteocalcin (OCN), a protein produced by bone and persisted in the brain, primes rapid visual escape response by increasing excitability of VTA GABAergic neuron subpopulation via OCN-GPR37-cAMP-THIK-1 (K _2P 13.1) pathway. Knock-out of OCN or its receptor GPR37, and conditional knock-out of GPR37 in VTA GABAergic or glutamatergic neurons caused delayed escape. Reconstituting OCN-GPR37 signaling specifically in VTA was sufficient to restore normal response. Single-cell transcriptomics combined with electrophysiology showed that OCN decreases potassium currents in a subpopulation of VTA GABAergic neurons via GPR37-induced cAMP reduction and subsequent THIK-1 suppression. This elevation of excitability in VTA neuron subpopulation can be recapitulated by HM4Di, an inhibitory chemogenetic GPCR commonly used to suppress neuronal activity. Our study demonstrated that visual behavior requires a bone-derived protein that tunes electrophysiology of central nervous system neurons. Graph In brief: The bone-brain axis regulates visual escape behavior. Osteocalcin (OCN), a small protein secreted by bone, plays a permissive role in rapid visual escape. This is achieved through GPR37 receptor expressed in a subpopulation of VTA GABAergic neurons. OCN-GPR37 signaling increases neuronal excitability by decreasing K+ current via THIK-1 channel suppression. Highlights: The bone-derived protein osteocalcin and its receptor GPR37 in VTA are required for rapid visual escape response. GPR37 is expressed in a subpopulation of VTA GABAergic neurons and primes rapid visual escape. Osteocalcin-GPR37 signaling increases neuronal excitability by suppressing THIK-1 (K _2P 13.1) channel via cAMP reduction. Activation of HM4Di increases excitability of subpopulation of VTA GABAergic neurons and enhances rapid visual escape.

Background: Mood disorders are very common among adolescents and include mainly bipolar disorder (BD) and major depressive disorder (MDD), with overlapping depressive symptoms that pose a significant challenge to realizing a rapid and accurate differential diagnosis in clinical practice. Misdiagnosis of BD as MDD can lead to inappropriate treatment and detrimental outcomes, including a poorer ultimate clinical and functional prognosis and even an increased risk of suicide. Therefore, it is of great significance for clinical management to identify clinical symptoms or features and biological markers that can accurately distinguish BD from MDD. With the aid of bibliometric analysis, we explore, visualize, and conclude the important directions of differential diagnostic studies of BD and MDD in adolescents.Materials and methods: A literature search was performed for studies on differential diagnostic studies of BD and MDD among adolescents in the Web of Science Core Collection database. All studies considered for this article were published between 2004 and 2023. Bibliometric analysis and visualization were performed using the VOSviewer and CiteSpace software.Results: In total, 148 publications were retrieved. The number of publications on differential diagnostic studies of BD and MDD among adolescents has been generally increasing since 2012, with the United States being an emerging hub with a growing influence in the field. Boris Birmaher is the top author in terms of the number of publications, and the Journal of Affective Disorders is the most published journal in the field. Co-occurrence analysis of keywords showed that clinical characteristics, genetic factors, and neuroimaging are current research hotspots. Ultimately, we comprehensively sorted out the current state of research in this area and proposed possible research directions in future.Conclusion: This is the first-ever study of bibliometric and visual analyses of differential diagnostic studies of BD and MDD in adolescents to reveal the current research status and important directions in the field. Our research and analysis results might provide some practical sources for academic scholars and clinical practice.

The ventral tegmental area (VTA) is a heterogeneous midbrain area that plays a significant role in diverse neural processes such as reward, aversion, and motivation. The VTA contains three main neuronal populations, namely, dopamine (DA), γ-aminobutyric acid (GABA), and glutamate neurons, but some neurons exhibit combinatorial molecular characteristics of dopaminergic, GABAergic, or glutamatergic neurons. However, little information is available regarding detailed distribution of neurons with single, double, and triple molecular characteristics of glutamatergic, dopaminergic, or GABAergic neurons in mice. We present a topographical distribution map of three main neuronal populations expressing a single molecular characteristic of dopaminergic, GABAergic, or glutamatergic neurons, and four neuronal populations co-expressing double or triple molecular characteristics in combinatorial manners, in the mouse VTA, following analysis of triple fluorescent in situ hybridization for the simultaneous detection of tyrosine hydroxylase (TH, marker for dopaminergic neurons), vesicular glutamate transporter 2 (VGLUT2, marker for glutamatergic neurons), and glutamic acid decarboxylase 2 (GAD2, marker for GABAergic neurons) mRNA. We found that the vast majority of neurons expressed a single type of mRNA, and these neurons were intermingled with neurons co-expressing double or triple combinations of VGLUT2, TH, or GAD2 in the VTA. These seven neuronal populations were differentially distributed in the VTA sub-nuclei across the rostro-caudal and latero-medial axes. This histochemical study will lead to a deeper understanding of the complexity of neuronal molecular characteristics in different VTA sub-nuclei, and potentially facilitate clarification of diverse functions of the VTA.

Glutamatergic and GABAergic neurons represent the neural components of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei (VN) in the maintenance of gait and balance by optogenetically stimulating the VN in VGluT2-cre and GAD2-cre mice. We demonstrate that glutamatergic, but not GABAergic VN neuronal subpopulation is responsible for immediate and strong posturo-locomotor deficits, comparable to unilateral vestibular deafferentation models. During optogenetic stimulation, the support surface dramatically increased in VN ^VGluT2+ mice, and rapidly fell back to baseline after stimulation, whilst it remained unchanged during similar stimulation of VN ^GAD2+ mice. This effect persisted when vestibular compensation was removed. Posturo-locomotor alterations evoked in VN ^VGluT2+ animals were still present immediately after stimulation, while they disappeared 1h later. Overall, these results indicate a fundamental role for VN ^VGluT2+ neurons in balance and posturo-locomotor functions, but not for VN ^GAD2+ neurons, in this specific context. This new optogenetic approach will be useful to characterize the role of the different VN neuronal populations involved in vestibular physiology and pathophysiology. Highlights: For the first time, Vestibular nuclei were optogenetically stimulated in free-moving animals, to asses for glutamatergic and GABAergic neurons functions in posturo-locomotor behaviors. Brief optogenetic activation of VNVGluT2+, but not VNGAD2+, induced immediate and strong postural deficit. Stimulation of VNVGluT2+ neurons provoked an imbalance with continuous effect on locomotion for a short period of time after stimulation. These results are comparable to the classical vestibular deafferentation models during their peak of deficit, and set optogenetic stimulation as a new model to study vestibular deficits.