Modulating mTOR-dependent astrocyte substate transitions to alleviate neurodegeneration.

Traditional approaches to studying astrocyte heterogeneity have mostly focused on analyzing static properties, failing to identify whether subtypes represent intermediate or final states of reactive astrocytes. Here we show that previously proposed neuroprotective and neurotoxic astrocytes are transitional states rather than distinct subtypes, as revealed through time-series multiomic sequencing. Neuroprotective astrocytes are an intermediate state of the transition from a nonreactive to a neurotoxic state in response to neuroinflammation, a process regulated by the mTOR signaling pathway.

Causal contributions of cell-type-specific circuits in the posterior dorsal striatum to auditory decision-making.

In the dorsal striatum (DS), the direct- and indirect-pathway striatal projection neurons (dSPNs and iSPNs) play crucial opposing roles in controlling actions. However, it remains unclear whether and how dSPNs and iSPNs provide distinct and specific contributions to decision-making, a process transforming sensory inputs to actions. Here, we perform causal interrogations on the roles of dSPNs and iSPNs in the posterior DS (pDS) in auditory-guided decision-making.

Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits.

Chronic methamphetamine (METH) use, a prevalent psychostimulant, is known to impair attention, yet the cellular mechanisms driving these deficits remain poorly understood. Here, we employed a rat model of repeated passive METH injections and evaluated attentional performance using the 5-choice serial reaction time task (5-CSRTT). Using single-nucleus RNA sequencing, immunofluorescence and in situ hybridization, we characterized the response of neurons in the reticulotegmental nucleus (RtTg) to METH exposure.

Dynamic ensemble balance in direct- and indirect-pathway striatal projection neurons underlying decision-related action selection.

The posterior dorsal striatum (pDS) plays an essential role in sensory-guided decision-making. However, it remains unclear how the antagonizing direct- and indirect-pathway striatal projection neurons (dSPNs and iSPNs) work in concert to support action selection. Here, we employed deep-brain two-photon imaging to investigate pathway-specific single-neuron and population representations during an auditory-guided decision-making task.

Causal role of frontocentral beta oscillation in comprehending linguistic communicative functions.

Linguistic communication is often considered as an action serving the function of conveying the speaker's goal to the addressee. Although neuroimaging studies have suggested a role of the motor system in comprehending communicative functions, the underlying mechanism is yet to be specified. Here, by two EEG experiments and a tACS experiment, we demonstrate that the frontocentral beta oscillation, which represents action states, plays a crucial part in linguistic communication understanding.

Activity of nested neural circuits drives different courtship songs in Drosophila.

Motor systems implement diverse motor programs to pattern behavioral sequences, yet how different motor actions are controlled on a moment-by-moment basis remains unclear. Here, we investigated the neural circuit mechanisms underlying the control of distinct courtship songs in Drosophila. Courting males rapidly alternate between two types of song: pulse and sine.

Heterozygous Variants in KCNJ10 Cause Paroxysmal Kinesigenic Dyskinesia Via Haploinsufficiency.

Objective: Most paroxysmal kinesigenic dyskinesia (PKD) cases are hereditary, yet approximately 60% of patients remain genetically undiagnosed. We undertook the present study to uncover the genetic basis for undiagnosed PKD patients.

Methods: Whole-exome sequencing was performed for 106 PRRT2-negative PKD probands.

Gapr for large-scale collaborative single-neuron reconstruction.

Whole-brain analysis of single-neuron morphology is crucial for unraveling the complex structure of the brain. However, large-scale neuron reconstruction from terabyte and even petabyte data of mammalian brains generated by state-of-the-art light microscopy is a daunting task. Here, we developed 'Gapr' (Gapr accelerates projectome reconstruction) that streamlines deep learning-based automatic reconstruction, 'automatic proofreading' that reduces human workloads at high-confidence sites, and high-throughput collaborative proofreading by crowd users through the Internet.

The role of periaqueductal gray astrocytes in anxiety-like behavior induced by acute stress.

Astrocytes in the central nervous system play a vital role in modulating synaptic transmission and neuronal activation by releasing gliotransmitters. The 5-HTergic neurons in the ventrolateral periaqueductal gray (vlPAG) are important in anxiety processing. However, it remains uncertain whether the regulation of astrocytic activity on vlPAG 5-HTergic neurons is involved in anxiety processing.

Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo.

The mouse auditory organ cochlea contains two types of sound receptors: inner hair cells (IHCs) and outer hair cells (OHCs). Tbx2 is expressed in IHCs but repressed in OHCs, and neonatal OHCs that misexpress Tbx2 transdifferentiate into IHC-like cells. However, the extent of this switch from OHCs to IHC-like cells and the underlying molecular mechanism remain poorly understood.

Predictability of cortico-cortical connections in the mammalian brain.

Despite a five order of magnitude range in size, the brains of mammals share many anatomical and functional characteristics that translate into cortical network commonalities. Here we develop a machine learning framework to quantify the degree of predictability of the weighted interareal cortical matrix. Partial network connectivity data were obtained with retrograde tract-tracing experiments generated with a consistent methodology, supplemented by projection length measurements in a nonhuman primate (macaque) and a rodent (mouse).

High-frequency neural activity dysregulation is associated with sleep and psychiatric disorders in BMAL1-deficient animal models.

Sleep disturbance led by BMAL1-deficiency has been recognized both in rodent and non-human primate models. Yet it remained unclear how their diurnal brain oscillations were affected upon BMAL1 ablation and what caused the discrepancy in the quantity of sleep between the two species. Here, we investigated diurnal electroencephalographs of BMAL1-deficient mice and cynomolgus monkeys at young adult age and uncovered a shared defect of dysregulated high-frequency oscillations by Kullback-Leibler divergence analysis.

Comparative transcriptome analysis between rhesus macaques ( ) and crab-eating macaques ( ).

Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques ( , MMU) and crab-eating macaques ( , MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored.

Deciphering the genetic interactions between Pou4f3, Gfi1, and Rbm24 in maintaining mouse cochlear hair cell survival.

Mammals harbor a limited number of sound-receptor hair cells (HCs) that cannot be regenerated after damage. Thus, investigating the underlying molecular mechanisms that maintain HC survival is crucial for preventing hearing impairment. Intriguingly, or HCs form initially but then rapidly degenerate, whereas HCs degenerate considerably later.

Combinatorial expression of γ-protocadherins regulates synaptic connectivity in the mouse neocortex.

In the process of synaptic formation, neurons must not only adhere to specific principles when selecting synaptic partners but also possess mechanisms to avoid undesirable connections. Yet, the strategies employed to prevent unwarranted associations have remained largely unknown. In our study, we have identified the pivotal role of combinatorial clustered protocadherin gamma (γ-PCDH) expression in orchestrating synaptic connectivity in the mouse neocortex.

High-throughput mapping of single-neuron projection and molecular features by retrograde barcoded labeling.

Deciphering patterns of connectivity between neurons in the brain is a critical step toward understanding brain function. Imaging-based neuroanatomical tracing identifies area-to-area or sparse neuron-to-neuron connectivity patterns, but with limited throughput. Barcode-based connectomics maps large numbers of single-neuron projections, but remains a challenge for jointly analyzing single-cell transcriptomics.

Volition motivates cognitive performance at the response-execution level by attenuating task-irrelevant motor activations.

Humans express volition by making voluntary choices which, relative to forced choices, can motivate cognitive performance in a variety of tasks. However, a task that requires the generation of motor responses on the basis of external sensory stimulation involves complex underlying cognitive processes, e.g.