Serotonergic modulation of vigilance states in zebrafish and mice.

Vigilance refers to being alertly watchful or paying sustained attention to avoid potential threats. Animals in vigilance states reduce locomotion and have an enhanced sensitivity to aversive stimuli so as to react quickly to dangers. Here we report that an unconventional 5-HT driven mechanism operating at neural circuit level which shapes the internal state underlying vigilance behavior in zebrafish and male mice.

Circuit reconstruction of newborn neurons after spinal cord injury in adult rats via an NT3-chitosan scaffold.

An implanted neurotrophin-3 (NT3)-chitosan scaffold can recruit endogenous neural stem cells to migrate to a lesion region and differentiate into mature neurons after adult spinal cord injury (SCI). However, the identities of these newborn neurons and whether they can form functional synapses and circuits to promote recovery after paraplegia remain unknown. By using combined advanced technologies, we revealed here that the newborn neurons of several subtypes received synaptic input from the corticospinal tract (CST), rubrospinal tract (RST), and supraspinal tracts.

De novo establishment of circuit modules restores locomotion after spinal cord injury in adult zebrafish.

Mechanisms underlying spontaneous locomotor recovery after spinal cord injury (SCI) remain unclear. Using adult zebrafish with complete SCI, we show that V2a interneurons regrow their axon to bridge the lesioned spinal segments in a subclass-specific and chronological order. Early after SCI, reestablishment of a unitary high-rhythm locomotor circuit is driven merely by axon-regrown fast V2a interneurons.

Shared nociceptive dorsal root ganglion neurons participating in acupoint sensitization.

When the body is under pathological stress (injury or disease), the status of associated acupoints changes, including decreased pain threshold. Such changes in acupoint from a "silent" to an "active" state are considered "acupoint sensitization," which has become an important indicator of acupoint selection. However, the mechanism of acupoint sensitization remains unclear.

An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebrafish.

Spinal cord injury (SCI) interrupts long-projecting descending spinal neurons and disrupts the spinal central pattern generator (CPG) that controls locomotion. The intrinsic mechanisms underlying re-wiring of spinal neural circuits and recovery of locomotion after SCI are unclear. Zebrafish shows axonal regeneration and functional recovery after SCI making it a robust model to study mechanisms of regeneration.

A specialized spinal circuit for command amplification and directionality during escape behavior.

In vertebrates, action selection often involves higher cognition entailing an evaluative process. However, urgent tasks, such as defensive escape, require an immediate implementation of the directionality of escape trajectory, necessitating local circuits. Here we reveal a specialized spinal circuit for the execution of escape direction in adult zebrafish.

A neuronal circuit that generates the temporal motor sequence for the defensive response in zebrafish larvae.

Animals use a precisely timed motor sequence to escape predators. This requires the nervous system to coordinate several motor behaviors and execute them in a temporal and smooth manner. We here describe a neuronal circuit that faithfully generates a defensive motor sequence in zebrafish larvae.

Multiple Rhythm-Generating Circuits Act in Tandem with Pacemaker Properties to Control the Start and Speed of Locomotion.

In vertebrates, specific command centers in the brain can selectively drive slow-explorative or fast-speed locomotion. However, it remains unclear how the locomotor central pattern generator (CPG) processes descending drive into coordinated locomotion. Here, we reveal, in adult zebrafish, a logic of the V2a interneuron rhythm-generating circuits involving recurrent and hierarchical connectivity that acts in tandem with pacemaker properties to provide an ignition and gear-shift mechanism to start locomotion and change speed.

Specialized cutaneous Schwann cells initiate pain sensation.

An essential prerequisite for the survival of an organism is the ability to detect and respond to aversive stimuli. Current belief is that noxious stimuli directly activate nociceptive sensory nerve endings in the skin. We discovered a specialized cutaneous glial cell type with extensive processes forming a mesh-like network in the subepidermal border of the skin that conveys noxious thermal and mechanical sensitivity.

WNT/NOTCH Pathway Is Essential for the Maintenance and Expansion of Human MGE Progenitors.

Medial ganglionic eminence (MGE)-like cells yielded from human pluripotent stem cells (hPSCs) hold great potentials for cell therapies of related neurological disorders. However, cues that orchestrate the maintenance versus differentiation of human MGE progenitors, and ways for large-scale expansion of these cells have not been investigated. Here, we report that WNT/CTNNB1 signaling plays an essential role in maintaining MGE-like cells derived from hPSCs.

Responsibility and Sustainability in Brain Science, Technology, and Neuroethics in China-a Culture-Oriented Perspective.

The China Brain Project is in development. Integrating an ethical framework to identify and assess ethical challenges and plan for solutions is a priority. Here Wang et al.

V2a interneuron diversity tailors spinal circuit organization to control the vigor of locomotor movements.

Locomotion is a complex motor task generated by spinal circuits driving motoneurons in a precise sequence to control the timing and vigor of movements, but the underlying circuit logic remains to be understood. Here we reveal, in adult zebrafish, how the diversity and selective distribution of two V2a interneuron types within the locomotor network transform commands into an appropriate, task-dependent circuit organization. Bursting-type V2a interneurons with unidirectional axons predominantly target distal dendrites of slow motoneurons to provide potent, non-linear excitation involving NMDA-dependent potentiation.

Multiple H sensors mediate the extracellular acidification-induced [Ca] elevation in cultured rat ventricular cardiomyocytes.

Acidosis has been known to cause "Ca transients", however, the mechanism is still uncertain. Here, we demonstrated that multiple H sensors, such as ASICs, TRPV1 and proton-sensing G protein coupled receptors (GPCRs) are involved in extracellular acidification-induced intracellular calcium ([Ca]) elevation. By using calcium imaging measures, we observed that both ASIC and TRPV1 channels inhibitors suppressed the [Ca] elevation induced by extracellular acidosis in cultured rat cardiac myocytes.

Motor neurons control locomotor circuit function retrogradely via gap junctions.

Motor neurons are the final stage of neural processing for the execution of motor behaviours. Traditionally, motor neurons have been viewed as the 'final common pathway', serving as passive recipients merely conveying to the muscles the final motor program generated by upstream interneuron circuits. Here we reveal an unforeseen role of motor neurons in controlling the locomotor circuit function via gap junctions in zebrafish.

A Hardwired Circuit Supplemented with Endocannabinoids Encodes Behavioral Choice in Zebrafish.

Animals constantly make behavioral choices to facilitate moving efficiently through their environment. When faced with a threat, animals make decisions in the midst of other ongoing behaviors through a context-dependent integration of sensory stimuli. In vertebrates, the mechanisms underlying behavioral selection are poorly understood.

Separate microcircuit modules of distinct v2a interneurons and motoneurons control the speed of locomotion.

Spinal circuits generate locomotion with variable speed as circumstances demand. These circuits have been assumed to convey equal and uniform excitation to all motoneurons whose input resistance dictates their activation sequence. However, the precise connectivity pattern between excitatory premotor circuits and the different motoneuron types has remained unclear.

Pattern of innervation and recruitment of different classes of motoneurons in adult zebrafish.

In vertebrates, spinal circuits drive rhythmic firing in motoneurons in the appropriate sequence to produce locomotor movements. These circuits become active early during development and mature gradually to acquire the flexibility necessary to accommodate the increased behavioral repertoire of adult animals. The focus here is to elucidate how different pools of motoneurons are organized and recruited and how membrane properties contribute to their mode of operation.

Gating the polarity of endocannabinoid-mediated synaptic plasticity by nitric oxide in the spinal locomotor network.

The final motor output underlying behavior arises from an appropriate balance between excitation and inhibition within neural networks. Retrograde signaling by endocannabinoids adapts synaptic strengths and the global activity of neural networks. In the spinal cord, endocannabinoids are mobilized postsynaptically from network neurons and act retrogradely on presynaptic cannabinoid receptors to potentiate the locomotor frequency.

Existence and distinction of acid-evoked currents in rat astrocytes.

Astrocytes are vital structures that support and/or protect neighboring neurons from pathology. Although it is generally accepted that glutamate receptors mediate most astrocyte effects, acid-evoked currents have recently attracted attention for their role in this regard. Here, we identified the existence and characteristics of acid-sensing ion channels (ASICs) and the transient receptor potential vanilloid type 1 (TRPV1) in astrocytes.