Neuroscience bulletin最新文献

Yes-associated protein (YAP), the key transcriptional co-factor and downstream effector of the Hippo pathway, has emerged as one of the primary regulators of neural as well as glial cells. It has been detected in various glial cell types, including Schwann cells and olfactory ensheathing cells in the peripheral nervous system, as well as radial glial cells, ependymal cells, Bergmann glia, retinal Müller cells, astrocytes, oligodendrocytes, and microglia in the central nervous system. With the development of neuroscience, understanding the functions of YAP in the physiological or pathological processes of glia is advancing. In this review, we aim to summarize the roles and underlying mechanisms of YAP in glia and glia-related neurological diseases in an integrated perspective.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.

The retrosplenial cortex has been implicated in processing sensory information and spatial learning, with abnormal neural activity reported in association with psychedelics and in mouse and non-human primate models of autism spectrum disorders (ASDs). The direct role of the retrosplenial cortex in regulating social behaviors remains unclear. In this work, we reveal that neural activity in the retrosplenial agranular cortex (RSA), a subregion of the retrosplenial cortex, is initially activated, then quickly suppressed upon social contact. This up-down phase of RSA neurons is crucial for normal social behaviors. Parvalbumin-positive GABAergic neurons in the hippocampal CA1 region were found to send inhibitory projections to the RSA. Blocking these CA1-RSA inhibitory inputs significantly impaired social behavior. Notably, enhancing the CA1-RSA inhibitory input rescued the social behavior defects in an ASD mouse model. This work suggests a neural mechanism for the salience processing of social behavior and identifies a potential target for ASD intervention using neural modulation approaches.

Psychiatric comorbidity is common in symptom-based diagnoses like autism spectrum disorder (ASD), attention/deficit hyper-activity disorder (ADHD), and obsessive-compulsive disorder (OCD). However, these co-occurring symptoms mediated by shared and/or distinct neural mechanisms are difficult to profile at the individual level. Capitalizing on unsupervised machine learning with a hierarchical Bayesian framework, we derived latent disease factors from resting-state functional connectivity data in a hybrid cohort of ASD and ADHD and delineated individual associations with dimensional symptoms based on canonical correlation analysis. Models based on the same factors generalized to previously unseen individuals in a subclinical cohort and one local OCD database with a subset of patients undergoing neurosurgical intervention. Four factors, identified as variably co-expressed in each patient, were significantly correlated with distinct symptom domains (r = -0.26-0.53, P < 0.05): behavioral regulation (Factor-1), communication (Factor-2), anxiety (Factor-3), adaptive behaviors (Factor-4). Moreover, we demonstrated Factor-1 expressed in patients with OCD and Factor-3 expressed in participants with anxiety, at the degree to which factor expression was significantly predictive of individual symptom scores (r = 0.18-0.5, P < 0.01). Importantly, peri-intervention changes in Factor-1 of OCD were associated with variable treatment outcomes (r = 0.39, P < 0.05). Our results indicate that these data-derived latent disease factors quantify individual factor expression to inform dimensional symptom and treatment outcomes across cohorts, which may promote quantitative psychiatric diagnosis and personalized intervention.

Conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins leads to the accumulation of 5hmC in the central nervous system; however, the role of 5hmC in the postnatal brain and how its levels and target genes are regulated by TETs remain elusive. We have generated mice that lack all three Tet genes specifically in postnatal excitatory neurons. These mice exhibit significantly reduced 5hmC levels, altered dendritic spine morphology within brain regions crucial for cognition, and substantially impaired spatial and associative memories. Transcriptome profiling combined with epigenetic mapping reveals that a subset of genes, which display changes in both 5hmC/5mC levels and expression patterns, are involved in synapse-related functions. Our findings provide insight into the role of postnatally accumulated 5hmC in the mouse brain and underscore the impact of 5hmC modification on the expression of genes essential for synapse development and function.

The insula is a complex brain region central to the orchestration of taste perception, interoception, emotion, and decision-making. Recent research has shed light on the intricate connections between the insula and other brain regions, revealing the crucial role of this area in integrating sensory, emotional, and cognitive information. The unique anatomical position and extensive connectivity allow the insula to serve as a critical hub in the functional network of the brain. We summarize its role in interoceptive and exteroceptive sensory processing, illustrating insular function as a bridge connecting internal and external experiences. Drawing on recent research, we delineate the insular involvement in emotional processes, highlighting its implications in psychiatric conditions, such as anxiety, depression, and addiction. We further discuss the insular contributions to cognition, focusing on its significant roles in time perception and decision-making. Collectively, the evidence underscores the insular function as a dynamic interface that synthesizes diverse inputs into coherent subjective experiences and decision-making processes. Through this review, we hope to highlight the importance of the insula as an interface between sensation, emotion, and cognition, and to inspire further research into this fascinating brain region.

Axon initial segment (AIS) is the most excitable subcellular domain of a neuron for action potential initiation. AISs of cortical projection neurons (PNs) receive GABAergic synaptic inputs primarily from chandelier cells (ChCs), which are believed to regulate action potential generation and modulate neuronal excitability. As individual ChCs often innervate hundreds of PNs, they may alter the activity of PN ensembles and even impact the entire neural network. During postnatal development or in response to changes in network activity, the AISs and axo-axonic synapses undergo dynamic structural and functional changes that underlie the wiring, refinement, and adaptation of cortical microcircuits. Here we briefly introduce the history of ChCs and review recent research advances employing modern genetic and molecular tools. Special attention will be attributed to the plasticity of the AIS and the ChC-PN connections, which play a pivotal role in shaping the dynamic network under both physiological and pathological conditions.

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by progressive axonopathy, jointly leading to the dying back of the motor neuron, disrupting both nerve signaling and motor control. In this review, we highlight the roles of axonopathy in ALS progression, driven by the interplay of multiple factors including defective trafficking machinery, protein aggregation, and mitochondrial dysfunction. Dysfunctional intracellular transport, caused by disruptions in microtubules, molecular motors, and adaptors, has been identified as a key contributor to disease progression. Aberrant protein aggregation involving TDP-43, FUS, SOD1, and dipeptide repeat proteins further amplifies neuronal toxicity. Mitochondrial defects lead to ATP depletion, oxidative stress, and Ca²⁺ imbalance, which are regarded as key factors underlying the loss of neuromuscular junctions and axonopathy. Mitigating these defects through interventions including neurotrophic treatments offers therapeutic potential. Collaborative research efforts aim to unravel ALS complexities, opening avenues for holistic interventions that target diverse pathological mechanisms.