Explore the vast range of titles available.

The possible existence of deeply-bound$\\bar K$ -nuclear bound states, kaonic nuclei, has been widely discussed as products of the strongly attractive$\\bar K$N interaction in I = 0 channels. Investigations of those exotic states will provide us unique information of the$\\bar K$N interaction below the threshold, which is still not fully understood so far. Recently, we observed the simplest kaonic nuclei,$\\bar K$NN , having a much deeper binding energy than normal nuclei via inflight ( K − , N ) reactions at the J-PARC E15 experiment. For further studies, we have proposed a series of experimental programs for the systematic investigation of light kaonic nuclei, from$\\bar K$N (Λ(1405)) to$\\bar K$NNNN . We will measure the$\\bar K$NNN ( A = 3) system at the new experiment approved as J-PARC E80, as a first step toward a comprehensive study.

The cerebellar involvement in cognitive functions such as attention, language, working memory, emotion, goal-directed behavior and spatial navigation is constantly growing. However, an exact connectivity map between the hippocampus and cerebellum in mice is still unknown. Here, we conducted a tracing study to identify the sequence of transsynaptic, cerebellar-hippocampal connections in the mouse brain using combinations of Recombinant adeno-associated virus (rAAV) and pseudotyped deletion-mutant rabies (RABV) viruses. Stereotaxic injection of a primarily anterograde rAAV-WGA (wheat germ agglutinin)-Cre tracer virus in the deep cerebellar nuclei (DCN) of a Cre-dependent tdTomato reporter mouse resulted in strong tdTomato labeling in hippocampal CA1 neurons, retrosplenial cortex (RSC), rhinal cortex (RC) as well as thalamic and cerebellar areas. Whereas hippocampal injections with the retrograde tracer virus rAAV-TTC (tetanus toxin C fragment)-eGFP, displayed eGFP positive cells in the rhinal cortex and subiculum. To determine the sequence of mono-transsynaptic connections between the cerebellum and hippocampus, we used the retrograde tracer RABVΔG-eGFP(EnvA). The tracing revealed a direct connection from the dentate gyrus (DG) in the hippocampus to the RSC, RC and subiculum (S), which are monosynaptically connected to thalamic laterodorsal and ventrolateral areas. These thalamic nuclei are directly connected to cerebellar fastigial (FN), interposed (IntP) and lateral (Lat) nuclei, discovering a new projection route from the fastigial to the laterodorsal thalamic nucleus in the mouse brain. Collectively, our findings suggest a new cerebellar-hippocampal connection the laterodorsal and ventrolateral thalamus to RSC, RC and S. These results strengthen the notion of the cerebellum's involvement in cognitive functions such as spatial navigation a polysynaptic circuitry.

In the basal ganglia (BG), anatomically segregated and topographically organized feedforward circuits are thought to modulate multiple behaviors in parallel. Although topographically arranged BG circuits have been described, the extent to which these relationships are maintained across the BG output nuclei and in downstream targets is unclear. Here, using focal trans-synaptic anterograde tracing, we show that the motor-action-related topographical organization of the striatum is preserved in all BG output nuclei. The topography is also maintained downstream of the BG and in multiple parallel closed loops that provide striatal input. Furthermore, focal activation of two distinct striatal regions induces either licking or turning, consistent with their respective anatomical targets of projection outside of the BG. Our results confirm the parallel model of BG function and suggest that the integration and competition of information relating to different behavior occur largely outside of the BG.This study demonstrates that basal ganglia functional topography is maintained across and downstream of its output nuclei, and in closed loops. Focal stimulation of distinct striatal subregions induces distinct action, supporting a model of parallel behavioral control.

Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate-modulating NMDA receptor antagonist ketamine. Targeting the glutamatergic system might thus provide a novel molecular strategy for antidepressant treatment. Since glutamate is the most abundant and major excitatory neurotransmitter in the brain, pathophysiological changes in glutamatergic signaling are likely to affect neurobehavioral plasticity, information processing and large-scale changes in functional brain connectivity underlying certain symptoms of major depressive disorder. Using resting state functional magnetic resonance imaging (rsfMRI), the \"dorsal nexus \"(DN) was recently identified as a bilateral dorsal medial prefrontal cortex region showing dramatically increased depression-associated functional connectivity with large portions of a cognitive control network (CCN), the default mode network (DMN), and a rostral affective network (AN). Hence, Sheline and colleagues (2010) proposed that reducing increased connectivity of the DN might play a critical role in reducing depression symptomatology and thus represent a potential therapy target for affective disorders. Here, using a randomized, placebo-controlled, double-blind, crossover rsfMRI challenge in healthy subjects we demonstrate that ketamine decreases functional connectivity of the DMN to the DN and to the pregenual anterior cingulate (PACC) and medioprefrontal cortex (MPFC) via its representative hub, the posterior cingulate cortex (PCC). These findings in healthy subjects may serve as a model to elucidate potential biomechanisms that are addressed by successful treatment of major depression. This notion is further supported by the temporal overlap of our observation of subacute functional network modulation after 24 hours with the peak of efficacy following an intravenous ketamine administration in treatment-resistant depression.

•Modafinil shapes the thalamo-cortical functional connectivity in a specific manner.•The medial pulvinar increased connectivity with Sensorimotor/Attention Networks.•The anterior + inferior pulvinar enhanced connectivity with the Attention Network.•Ventral complex increased connectivity with the Default Mode/FrontoParietal Networks.•Connectivity changes overlap with the expression of 5-HT, mGluR5 receptors, and NET. Modafinil promotes wakefulness and enhances cognitive function through mechanisms and neural effects that are still partially unknown. Several studies have shown that the compound alters the functional cortical architecture. In contrast, its influence on subcortical regions and thalamocortical connections, which are crucial for modulating neocortical connectivity, remains unexplored. The acute modulation of thalamo-cortical connectivity was assessed in two groups of participants who received either a single 100 mg dose of modafinil (N = 25) or a placebo (N = 25). Magnetic Resonance Imaging (MRI) was used to parcel the thalamus into its constituent nuclei, which served as seeds for voxel-wise resting state functional connectivity analyses. Additionally, maps of nuclei-specific functional reorganization were compared to those of receptor/transporter expression to assess their spatial overlaps. Modafinil, but not placebo, altered the connectivity of three thalamic nuclei. Specifically, the medial pulvinar nuclei showed increased connectivity with cortical regions of the Sensorimotor and Salience/Ventral Attention (SVAN) Networks. These functional changes spatially overlapped with the distribution of the norepinephrine transporter (NET). Additionally, the anterior and inferior pulvinar complex exhibited enhanced connectivity with the insular and supramarginal regions of the SVAN and superior frontal area of the Default Mode Network (DMN). However, unlike the medial pulvinar, these effects were not spatially linked to the expression of any specific receptor or transporter. Finally, the ventro-lateral anterior complex exhibited increased connectivity with the posterior region of the DMN and the Fronto-Parietal Control Network, along with decreased connectivity to the premotor cortex. The topography of these functional modifications mainly overlaps with the distribution of glutamatergic and serotonergic receptors. In summary, our findings highlight modafinil's influence on thalamocortical circuits, emphasizing the role of higher-order pulvinar nuclei and ventro-lateral anterior complex.

The cerebral cortex is organized into specialized sensory areas, whose initial territory is determined by intracortical molecular determinants. Yet, sensory cortical area size appears to be fine tuned during development to respond to functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates the cortical areas size in mice. This mechanism is mediated by spontaneous thalamic calcium waves that propagate among sensory-modality thalamic nuclei up to the cortex and that provide a means of communication among sensory systems. Wave pattern alterations in one nucleus lead to changes in the pattern of the remaining ones, triggering changes in thalamic gene expression and cortical area size. Thus, silencing calcium waves in the auditory thalamus induces Rorβ upregulation in a neighbouring somatosensory nucleus preluding the enlargement of the barrel-field. These findings reveal that embryonic thalamic calcium waves coordinate cortical sensory area patterning and plasticity prior to sensory information processing. How sensory maps are formed in the brain is only partially understood. Here the authors describe spontaneous calcium waves that propagate across different sensory nuclei in the embryonic thalamus; disrupting the wave pattern triggers thalamic gene expression changes and eventually alters the size of cortical areas.

The “non-specific” ventromedial thalamic nucleus (VM) has long been considered a candidate for mediating cortical arousal due to its diffuse, superficial projections, but direct evidence was lacking. Here, we show in mice that the activity of VM calbindin1-positive matrix cells is high in wake and REM sleep and low in NREM sleep, and increases before cortical activity at the sleep-to-wake transition. Optogenetic stimulation of VM cells rapidly awoke all mice from NREM sleep and consistently caused EEG activation during slow wave anesthesia, while arousal did not occur from REM sleep. Conversely, chemogenetic inhibition of VM decreased wake duration. Optogenetic activation of the “specific” ventral posteromedial nucleus (VPM) did not cause arousal from either NREM or REM sleep. Thus, matrix cells in VM produce arousal and broad cortical activation during NREM sleep and slow wave anesthesia in a way that accounts for the effects classically attributed to “non-specific” thalamic nuclei. The ventromedial thalamus (VM) is thought to control cortical arousal through its diffuse projections to cortex. Here the authors record and manipulate the activity of calbindin1-positive matrix cells in VM and show that they bidirectionally regulate the sleep-wake transition.

The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, regulates thalamocortical interactions that are critical for sensory processing, attention and cognition 1 – 5 . TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders 6 – 9 . However, little is known about the organizational principles that underlie its divergent functions. Here we performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that cellular heterogeneity in the TRN is characterized by a transcriptomic gradient of two negatively correlated gene-expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core or shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections with the functionally distinct first-order and higher-order thalamic nuclei to form molecularly defined TRN–thalamus subnetworks. Selective perturbation of the two subnetworks in vivo revealed their differential role in regulating sleep. In sum, our study provides a comprehensive atlas of TRN neurons at single-cell resolution and links molecularly defined subnetworks to the functional organization of thalamocortical circuits. A study integrating single-cell RNA-sequencing and electrophysiology data shows that in mouse, the cellular repertoire of the thalamic reticular nucleus is characterized by a transcriptomic gradient defined at its extremes by mutually exclusive expression of Spp1 and Ecel1 , providing insights into the organizational principles underlying the divergent functions of this brain region.

Thalamocortical dysrhythmia is a key pathology of chronic neuropathic pain, but few studies have investigated thalamocortical networks in chronic low back pain (cLBP) given its non-specific etiology and complexity. Using fMRI, we propose an analytical pipeline to identify abnormal thalamocortical network dynamics in cLBP patients and validate the findings in two independent cohorts. We first identify two reoccurring dynamic connectivity states and their associations with chronic and temporary pain. Further analyses show that cLBP patients have abnormal connectivity between the ventral lateral/posterolateral nucleus (VL/VPL) and postcentral gyrus (PoCG) and between the dorsal/ventral medial nucleus and insula in the less frequent connectivity state, and temporary pain exacerbation alters connectivity between the VL/VPL and PoCG and the default mode network in the more frequent connectivity state. These results extend current findings on thalamocortical dysfunction and dysrhythmia in chronic pain and demonstrate that cLBP pathophysiology and clinical pain intensity are associated with distinct thalamocortical network dynamics. Thalamocortical dysrhythmia is a key pathology of chronic pain. Here, the authors propose an analytical pipeline to study dynamic fMRI brain networks and demonstrate that chronic low back pain pathophysiology and clinical pain intensity are associated with distinct thalamocortical network dynamics.

Pulmonary and heart failure are considered the primary causes of COVID-19-associated death, but the precise pathology of disease progression is unknown. [...]recent reports describe irregularities in coagulation for a subset of patients.1 Here we report the findings of autopsies of six patients (four men and two women, aged 58–82 years) who died from COVID-19 in April, 2020. Abundant experimental and animal model evidence of a neurogenic pathway for SARS CoV-2 via olfactory (CN I), trigeminal nerves (CN V), and the brainstem nuclei led us to look for evidence of localised brainstem alterations.4 In all brains examined, we observed localised perivascular and interstitial encephalitis with neuronal cell loss and axon degeneration in the dorsal motor nuclei of the vagus nerve, CN V, nucleus tractus solitarii, dorsal raphe nuclei, and fasciculus longitudinalis medialis, but no territorial infarctions (appendix). The most prominent changes were those of a diffuse alveolar damage with virus-induced epithelial changes, capillaritis, and organising pneumonia without interstitial collagen deposition.3,5,6 Intranuclear inclusion bodies were not observed.