Study on Shenbao Tablet in Treating Kidney-yang Deficiency Syndromebased on Metabolomics.

Aim: The aim of this study was to elucidate the mechanism of action of Shenbao tablets using metabolomics approach.

Background: Kidney-Yang deficiency is a common syndrome type in traditional Chinese Medicine (TCM) syndrome typology, closely related to disorders of multiple metabolic pathways and is the root cause and underlying syndrome type of many diseases. Shenbao tablets can significantly improve the main symptoms of kidney yang deficiency syndrome, but the mechanism of action of Shenbao tablets on kidney yang deficiency syndrome is still unknown.

Brainstem control of vocalization and its coordination with respiration.

Phonation critically depends on precise controls of laryngeal muscles in coordination with ongoing respiration. However, the neural mechanisms governing these processes remain unclear. We identified excitatory vocalization-specific laryngeal premotor neurons located in the retroambiguus nucleus (RAm) in adult mice as being both necessary and sufficient for driving vocal cord closure and eliciting mouse ultrasonic vocalizations (USVs).

General Anesthesia Activates a Central Anxiolytic Center in the BNST.

Unlabelled: Low doses of general anesthetics like ketamine and dexmedetomidine have anxiolytic properties independent of their sedative effects. How these different drugs exert these anxiolytic effects is not well understood. We discovered a population of GABAergic neurons in the oval division of the bed nucleus of the stria terminalis that is activated by multiple anesthetics and the anxiolytic drug diazepam (ovBNST ).

Brainstem premotor mechanisms underlying vocal production and vocal-respiratory coordination.

Unlabelled: Speech generation critically depends on precise controls of laryngeal muscles and coordination with ongoing respiratory activity. However, the neural mechanisms governing these processes remain unknown. Here, we mapped laryngeal premotor circuitry in adult mice and viral-genetically identified excitatory vocal premotor neurons located in the retroambiguus nucleus (RAm ) as both necessary and sufficient for driving vocal-cord closure and eliciting mouse ultrasonic vocalizations (USVs).

Somatosensory cortical signature of facial nociception and vibrotactile touch-induced analgesia.

Pain relief by vibrotactile touch is a common human experience. Previous neurophysiological investigations of its underlying mechanism in animals focused on spinal circuits, while human studies suggested the involvement of supraspinal pathways. Here, we examine the role of primary somatosensory cortex (S1) in touch-induced mechanical and heat analgesia.

Constructing an adult orofacial premotor atlas in Allen mouse CCF.

Premotor circuits in the brainstem project to pools of orofacial motoneurons to execute essential motor action such as licking, chewing, breathing, and in rodent, whisking. Previous transsynaptic tracing studies only mapped orofacial premotor circuits in neonatal mice, but the adult circuits remain unknown as a consequence of technical difficulties. Here, we developed a three-step monosynaptic transsynaptic tracing strategy to identify premotor neurons controlling vibrissa, tongue protrusion, and jaw-closing muscles in the adult mouse.

Recurrent circuitry is required to stabilize piriform cortex odor representations across brain states.

Pattern completion, or the ability to retrieve stable neural activity patterns from noisy or partial cues, is a fundamental feature of memory. Theoretical studies indicate that recurrently connected auto-associative or discrete attractor networks can perform this process. Although pattern completion and attractor dynamics have been observed in various recurrent neural circuits, the role recurrent circuitry plays in implementing these processes remains unclear.

General anesthetics activate a potent central pain-suppression circuit in the amygdala.

General anesthesia (GA) can produce analgesia (loss of pain) independent of inducing loss of consciousness, but the underlying mechanisms remain unclear. We hypothesized that GA suppresses pain in part by activating supraspinal analgesic circuits. We discovered a distinct population of GABAergic neurons activated by GA in the mouse central amygdala (CeA neurons).

Identifying Parabrachial Neurons Selectively Regulating Satiety for Highly Palatable Food in Mice.

Food consumption is necessary for organisms to maintain metabolic homeostasis. Both extrinsic and intrinsic processes, relayed via intricate neural circuitry, orchestrate the initiation and termination of food intake. More specifically, there are functionally distinct neural circuits that mediate either homeostatic or hedonic suppression of feeding.

A Specialized Neural Circuit Gates Social Vocalizations in the Mouse.

Vocalizations are fundamental to mammalian communication, but the underlying neural circuits await detailed characterization. Here, we used an intersectional genetic method to label and manipulate neurons in the midbrain periaqueductal gray (PAG) that are transiently active in male mice when they produce ultrasonic courtship vocalizations (USVs). Genetic silencing of PAG-USV neurons rendered males unable to produce USVs and impaired their ability to attract females.

A Common Neuroendocrine Substrate for Diverse General Anesthetics and Sleep.

How general anesthesia (GA) induces loss of consciousness remains unclear, and whether diverse anesthetic drugs and sleep share a common neural pathway is unknown. Previous studies have revealed that many GA drugs inhibit neural activity through targeting GABA receptors. Here, using Fos staining, ex vivo brain slice recording, and in vivo multi-channel electrophysiology, we discovered a core ensemble of hypothalamic neurons in and near the supraoptic nucleus, consisting primarily of neuroendocrine cells, which are persistently and commonly activated by multiple classes of GA drugs.

Publisher Correction: A craniofacial-specific monosynaptic circuit enables heightened affective pain.

In the version of this article initially published, ORCID links were missing for authors Erica Rodriguez, Koji Toda and Fan Wang. The error has been corrected in the HTML and PDF versions of the article.

A craniofacial-specific monosynaptic circuit enables heightened affective pain.

Humans often rank craniofacial pain as more severe than body pain. Evidence suggests that a stimulus of the same intensity induces stronger pain in the face than in the body. However, the underlying neural circuitry for the differential processing of facial versus bodily pain remains unknown.

Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit.

We developed a technology (capturing activated neuronal ensembles [CANE]) to label, manipulate, and transsynaptically trace neural circuits that are transiently activated in behavioral contexts with high efficiency and temporal precision. CANE consists of a knockin mouse and engineered viruses designed to specifically infect activated neurons. Using CANE, we selectively labeled neurons that were activated by either fearful or aggressive social encounters in a hypothalamic subnucleus previously known as a locus for aggression, and discovered that social-fear and aggression neurons are intermixed but largely distinct.

Supratrigeminal Bilaterally Projecting Neurons Maintain Basal Tone and Enable Bilateral Phasic Activation of Jaw-Closing Muscles.

Unlabelled: Anatomical studies have identified brainstem neurons that project bilaterally to left and right oromotor pools, which could potentially mediate bilateral muscle coordination. We use retrograde lentiviruses combined with a split-intein-mediated split-Cre-recombinase system in mice to isolate, characterize, and manipulate a population of neurons projecting to both the left and right jaw-closing trigeminal motoneurons. We find that these bilaterally projecting premotor neurons (BPNs) reside primarily in the supratrigeminal nucleus (SupV) and the parvicellular and intermediate reticular regions dorsal to the facial motor nucleus.

Identifying local and descending inputs for primary sensory neurons.

Primary pain and touch sensory neurons not only detect internal and external sensory stimuli, but also receive inputs from other neurons. However, the neuronal derived inputs for primary neurons have not been systematically identified. Using a monosynaptic rabies viruses-based transneuronal tracing method combined with sensory-specific Cre-drivers, we found that sensory neurons receive intraganglion, intraspinal, and supraspinal inputs, the latter of which are mainly derived from the rostroventral medulla (RVM).

Monosynaptic premotor circuit tracing reveals neural substrates for oro-motor coordination.

Feeding behaviors require intricately coordinated activation among the muscles of the jaw, tongue, and face, but the neural anatomical substrates underlying such coordination remain unclear. In this study, we investigate whether the premotor circuitry of jaw and tongue motoneurons contain elements for coordination. Using a modified monosynaptic rabies virus-based transsynaptic tracing strategy, we systematically mapped premotor neurons for the jaw-closing masseter muscle and the tongue-protruding genioglossus muscle.

The organization of submodality-specific touch afferent inputs in the vibrissa column.

The rodent tactile vibrissae are innervated by several different types of touch sensory neurons. The central afferents of all touch neurons from one vibrissa collectively project to a columnar structure called a barrelette in the brainstem. Delineating how distinct types of sensors connect to second-order neurons within each barrelette is critical for understanding tactile information coding and processing.

Loss of NR1 subunit of NMDARs in primary sensory neurons leads to hyperexcitability and pain hypersensitivity: involvement of Ca(2+)-activated small conductance potassium channels.

It is well established that activation of NMDARs plays an essential role in spinal cord synaptic plasticity (i.e., central sensitization) and pain hypersensitivity after tissue injury.

Generation and characterization of Tmeff2 mutant mice.

TMEFF2 is a single-transmembrane protein containing one EGF-like and two follistatin-like domains. Some studies implicated TMEFF2 as a tumor suppressor for prostate and other cancers, whereas others reported TMEFF2 functioning as a growth factor for neurons and other cells. To gain insights into the apparently conflicting roles of TMEFF2, we generated a null allele of Tmeff2 gene by replacing its first coding exon with human placental alkaline phosphatase cDNA (Tmeff2(PLAP)).

Intersectional Cre driver lines generated using split-intein mediated split-Cre reconstitution.

Tissue and cell type highly specific Cre drivers are very rare due to the fact that most genes or promoters used to direct Cre expressions are generally expressed in more than one tissues and/or in multiple cell types. We developed a split-intein based split-Cre system for highly efficient Cre-reconstitution through protein splicing. This split-intein-split-Cre system can be used to intersect the expression patterns of two genes or promoters to restrict full-length Cre reconstitution in their overlapping domains.

Proper formation of whisker barrelettes requires periphery-derived Smad4-dependent TGF-beta signaling.

Mammalian somatosensory topographic maps contain specialized neuronal structures that precisely recapitulate the spatial pattern of peripheral sensory organs. In the mouse, whiskers are orderly mapped onto several brainstem nuclei as a set of modular structures termed barrelettes. Using a dual-color iontophoretic labeling strategy, we found that the precise topography of barrelettes is not a result of ordered positions of sensory neurons within the ganglion.

Deletion of PIK3C3/Vps34 in sensory neurons causes rapid neurodegeneration by disrupting the endosomal but not the autophagic pathway.

The lipid kinase PIK3C3 (also called Vps34) regulates both the endosomal and autophagic pathways. However, the effect of inactivating PIK3C3 on neuronal endosomal versus autophagic processes in vivo has not been studied. We generated mice in which Pik3c3 was conditionally deleted in differentiated sensory neurons.

Analyzing somatosensory axon projections with the sensory neuron-specific Advillin gene.

Peripheral sensory neurons detect diverse physical stimuli and transmit the information into the CNS. At present, the genetic tools for specifically studying the development, plasticity, and regeneration of the sensory axon projections are limited. We found that the gene encoding Advillin, an actin binding protein that belongs to the gelsolin superfamily, is expressed almost exclusively in peripheral sensory neurons.