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).

CellBoost: A pipeline for machine assisted annotation in Neuroanatomy.

One of the important yet labor intensive tasks in neuroanatomy is the identification of select populations of cells. Current high-throughput techniques enable marking cells with histochemical fluorescent molecules as well as through the genetic expression of fluorescent proteins. Modern scanning microscopes allow high resolution multi-channel imaging of the mechanically or optically sectioned brain with thousands of marked cells per square millimeter.

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.

Theory of hierarchically organized neuronal oscillator dynamics that mediate rodent rhythmic whisking.

Rodents explore their environment through coordinated orofacial motor actions, including whisking. Whisking can free-run via an oscillator of inhibitory neurons in the medulla and can be paced by breathing. Yet, the mechanics of the whisking oscillator and its interaction with breathing remain to be understood.

The whisking oscillator circuit.

Central oscillators are primordial neural circuits that generate and control rhythmic movements. Mechanistic understanding of these circuits requires genetic identification of the oscillator neurons and their synaptic connections to enable targeted electrophysiological recording and causal manipulation during behaviours. However, such targeting remains a challenge with mammalian systems.

Trans-Seq maps a selective mammalian retinotectal synapse instructed by Nephronectin.

The mouse visual system serves as an accessible model to understand mammalian circuit wiring. Despite rich knowledge in retinal circuits, the long-range connectivity map from distinct retinal ganglion cell (RGC) types to diverse brain neuron types remains unknown. In this study, we developed an integrated approach, called Trans-Seq, to map RGCs to superior collicular (SC) circuits.

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.

Chronic loss of inhibition in piriform cortex following brief, daily optogenetic stimulation.

It is well established that seizures beget seizures, yet the cellular processes that underlie progressive epileptogenesis remain unclear. Here, we use optogenetics to briefly activate targeted populations of mouse piriform cortex (PCx) principal neurons in vivo. After just 3 or 4 days of stimulation, previously subconvulsive stimuli trigger massive, generalized seizures.

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.

Advillin Is Expressed in All Adult Neural Crest-Derived Neurons.

Promoter-based genetic recombination (via, e.g., Cre-lox) is most useful when all cells of interest express a particular gene.

Parallel Inhibitory and Excitatory Trigemino-Facial Feedback Circuitry for Reflexive Vibrissa Movement.

Animals employ active touch to optimize the acuity of their tactile sensors. Prior experimental results and models lead to the hypothesis that sensory inputs are used in a recurrent manner to tune the position of the sensors. A combination of electrophysiology, intersectional genetic viral labeling and manipulation, and classical tracing allowed us to identify second-order sensorimotor loops that control vibrissa movements by rodents.

Vibrissa sensory neurons: Linking distinct morphology to specific physiology and function.

Rodents use an array of long tactile facial hairs, the vibrissae, to locate and discriminate objects. Each vibrissa is densely innervated by multiple different types of trigeminal (TG) sensory neurons. Based on the sensory ending morphology, there are at least six types of vibrissa innervating neurons; whereas based on electrophysiological recordings, vibrissa neurons are generally classified as rapidly adapting (RA) and slowly adapting (SA), and show different responses to whisking movement and/or touch.

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.

Inhibition, Not Excitation, Drives Rhythmic Whisking.

Sniffing and whisking typify the exploratory behavior of rodents. These actions involve separate oscillators in the medulla, located respectively in the pre-Bötzinger complex (preBötC) and the vibrissa-related region of the intermediate reticular formation (vIRt). We examine how these oscillators synergize to control sniffing and whisking.

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.

A circuit for motor cortical modulation of auditory cortical activity.

Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex.

Subcellular localization of dystrophin isoforms in cardiomyocytes and phenotypic analysis of dystrophin-deficient mice reveal cardiac myopathy is predominantly caused by a deficiency in full-length dystrophin.

Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive muscle degenerative disorder that causes dilated cardiomyopathy in the second decade of life in affected males. Dystrophin, the gene responsible for DMD, encodes full-length dystrophin and various short dystrophin isoforms. In the mouse heart, full-length dystrophin Dp427 and a short dystrophin isoform, Dp71, are expressed.

New modules are added to vibrissal premotor circuitry with the emergence of exploratory whisking.

Rodents begin to use bilaterally coordinated, rhythmic sweeping of their vibrissae ("whisking") for environmental exploration around 2 weeks after birth. Whether (and how) the vibrissal control circuitry changes after birth is unknown, and the relevant premotor circuitry remains poorly characterized. Using a modified rabies virus transsynaptic tracing strategy, we labeled neurons synapsing directly onto vibrissa facial motor neurons (vFMNs).

Axonally translated SMADs link up BDNF and retrograde BMP signaling.

Axonal target-derived BMP and neurotrophin signaling are both known to regulate neuronal gene expression, differentiation, and axon growth. In this issue of Neuron, Ji and Jaffrey (2012) discovered that BMP-signaling endosomes depend on BDNF-induced axonal synthesis of SMADs to retrogradely regulate transcription in developing trigeminal neurons, providing a mechanism of integrating the two target-derived signals.

The mammalian class 3 PI3K (PIK3C3) is required for early embryogenesis and cell proliferation.

The Pik3c3 gene encodes an 887 amino acid lipid kinase, phosphoinositide-3-kinase class 3 (PIK3C3). PIK3C3 is known to regulate various intracellular membrane trafficking events. However, little is known about its functions during early embryogenesis in mammals.

Spatially and temporally regulated expression of specific heparan sulfate epitopes in the developing mouse olfactory system.

Heparan sulfate (HS) comprises a structurally diverse group of glycosaminoglycans present ubiquitously on cell surfaces and in the extracellular matrix. The spatially and temporally regulated expression of specific HS structures is essential for various developmental processes in the nervous system but their distributions in the mouse olfactory system have not been explored. Here, we examined the spatiotemporal distribution of particular HS species in the developing mouse olfactory system using three structure-specific monoclonal antibodies (HepSS-1, JM403 and NAH46).