Upregulation of breathing rate during running exercise by central locomotor circuits in mice.

While respiratory adaptation to exercise is compulsory to cope with the increased metabolic demand, the neural signals at stake remain poorly identified. Using neural circuit tracing and activity interference strategies in mice, we uncover here two systems by which the central locomotor network can enable respiratory augmentation in relation to running activity. One originates in the mesencephalic locomotor region (MLR), a conserved locomotor controller.

Mafa-dependent GABAergic activity promotes mouse neonatal apneas.

While apneas are associated with multiple pathological and fatal conditions, the underlying molecular mechanisms remain elusive. We report that a mutated form of the transcription factor Mafa (Mafa) that prevents phosphorylation of the Mafa protein leads to an abnormally high incidence of breath holding apneas and death in newborn Mafa mutant mice. This apneic breathing is phenocopied by restricting the mutation to central GABAergic inhibitory neurons and by activation of inhibitory Mafa neurons while reversed by inhibiting GABAergic transmission centrally.

A novel reticular node in the brainstem synchronizes neonatal mouse crying with breathing.

Human speech can be divided into short, rhythmically timed elements, similar to syllables within words. Even our cries and laughs, as well as the vocalizations of other species, are periodic. However, the cellular and molecular mechanisms underlying the tempo of mammalian vocalizations remain unknown.

A medullary centre for lapping in mice.

It has long been known that orofacial movements for feeding can be triggered, coordinated, and often rhythmically organized at the level of the brainstem, without input from higher centers. We uncover two nuclei that can organize the movements for ingesting fluids in mice. These neuronal groups, IRt and Peri5, are marked by expression of the pan-autonomic homeobox gene Phox2b and are located, respectively, in the intermediate reticular formation of the medulla and around the motor nucleus of the trigeminal nerve.

Calculation of Spectral Optical Constants Using Combined Ellipsometric and Reflectance Methods for Smooth and Rough Bulk Samples.

Spectra of the optical constants and of a substance are often deduced from spectroscopic measurements, performed on a thick and homogeneous sample, and from a model used to simulate these measurements. Spectra obtained for and using the ellipsometric method generally produce polarized reflectance simulations in strong agreement with the experimental measurements, but they sometimes introduce significant discrepancies over limited spectral ranges, whereas spectra of and obtained with the single-angle reflectance method require a perfectly smooth sample surface to be viable. This paper presents an alternative method to calculate and .

Absent phasing of respiratory and locomotor rhythms in running mice.

Examining whether and how the rhythms of limb and breathing movements interact is highly informative about the mechanistic origin of hyperpnoea during running exercise. However, studies have failed to reveal regularities. In particular, whether breathing frequency is inherently proportional to limb velocity and imposed by a synchronization of breaths to strides is still unclear.

Improved Infrared Optical Constants from Pressed Pellets: II. Ellipsometric and Values for Ammonium Sulfate with Variability Analysis.

Infrared reflectance analysis is facilitated via the comparison of spectra recorded in situ to a databank of actual or synthetic infrared reflectance spectra. It has recently been shown that reference spectra corresponding to the many different morphological forms of the same chemical can be generated synthetically using the imaginary, , and real, , components of the complex refractive index,  =  + i. One method to obtain the and vectors is infrared ellipsometry, which measures the changes in amplitude, tan Ψ, and phase, Δ, of polarized light reflected from the sample both as a function of wavenumber and angle of incidence.

Teashirt 1 (Tshz1) is essential for the development, survival and function of hypoglossal and phrenic motor neurons in mouse.

Feeding and breathing are essential motor functions and rely on the activity of hypoglossal and phrenic motor neurons that innervate the tongue and diaphragm, respectively. Little is known about the genetic programs that control the development of these neuronal subtypes. The transcription factor Tshz1 is strongly and persistently expressed in developing hypoglossal and phrenic motor neurons.

Mutation in precludes transcription factor cooperativity and causes congenital hypoventilation in humans and mice.

The respiratory rhythm is generated by the preBötzinger complex in the medulla oblongata, and is modulated by neurons in the retrotrapezoid nucleus (RTN), which are essential for accelerating respiration in response to high CO Here we identify a frameshift ( ) mutation in patients with congenital central hypoventilation. The mutation alters the C-terminal but not the DNA-binding domain of Mice with the analogous mutation recapitulate the breathing deficits found in humans. Furthermore, the mutation only interferes with a small subset of Lbx1 functions, and in particular with development of RTN neurons that coexpress Lbx1 and Phox2b.

Computer-aided neurophysiology and imaging with open-source PhysImage.

Improved integration between imaging and electrophysiological data has become increasingly critical for rapid interpretation and intervention as approaches have advanced in recent years. Here, we present PhysImage, a fork of the popular public-domain ImageJ that provides a platform for working with these disparate sources of data, and we illustrate its utility using in vitro preparations from murine embryonic and neonatal tissue. PhysImage expands ImageJ's core features beyond an imaging program by facilitating integration, analyses, and display of 2D waveform data, among other new features.

A V0 core neuronal circuit for inspiration.

Breathing in mammals relies on permanent rhythmic and bilaterally synchronized contractions of inspiratory pump muscles. These motor drives emerge from interactions between critical sets of brainstem neurons whose origins and synaptic ordered organization remain obscure. Here, we show, using a virus-based transsynaptic tracing strategy from the diaphragm muscle in the mouse, that the principal inspiratory premotor neurons share V0 identity with, and are connected by, neurons of the preBötzinger complex that paces inspiration.

Genetic identification of a hindbrain nucleus essential for innate vocalization.

Vocalization in young mice is an innate response to isolation or mechanical stimulation. Neuronal circuits that control vocalization and breathing overlap and rely on motor neurons that innervate laryngeal and expiratory muscles, but the brain center that coordinates these motor neurons has not been identified. Here, we show that the hindbrain nucleus tractus solitarius (NTS) is essential for vocalization in mice.

Robust network oscillations during mammalian respiratory rhythm generation driven by synaptic dynamics.

How might synaptic dynamics generate synchronous oscillations in neuronal networks? We address this question in the preBötzinger complex (preBötC), a brainstem neural network that paces robust, yet labile, inspiration in mammals. The preBötC is composed of a few hundred neurons that alternate bursting activity with silent periods, but the mechanism underlying this vital rhythm remains elusive. Using a computational approach to model a randomly connected neuronal network that relies on short-term synaptic facilitation (SF) and depression (SD), we show that synaptic fluctuations can initiate population activities through recurrent excitation.

The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO₂.

Maintaining constant CO2 and H(+) concentrations in the arterial blood is critical for life. The principal mechanism through which this is achieved in mammals is the respiratory chemoreflex whose circuitry is still elusive. A candidate element of this circuitry is the retrotrapezoid nucleus (RTN), a collection of neurons at the ventral medullary surface that are activated by increased CO2 or low pH and project to the respiratory rhythm generator.

Emergence of sigh rhythmogenesis in the embryonic mouse.

In mammals, eupnoeic breathing is periodically interrupted by spontaneous augmented breaths (sighs) that include a larger-amplitude inspiratory effort, typically followed by a post-sigh apnoea. Previous in vitro studies in newborn rodents have demonstrated that the respiratory oscillator of the pre-Bötzinger complex (preBötC) can generate the distinct inspiratory motor patterns for both eupnoea- and sigh-related behaviour. During mouse embryonic development, the preBötC begins to generate eupnoeic rhythmicity at embryonic day (E) 15.

Dual-mode operation of neuronal networks involved in left-right alternation.

All forms of locomotion are repetitive motor activities that require coordinated bilateral activation of muscles. The executive elements of locomotor control are networks of spinal neurons that determine gait pattern through the sequential activation of motor-neuron pools on either side of the body axis. However, little is known about the constraints that link left-right coordination to locomotor speed.

Ancient origin of somatic and visceral neurons.

Background: A key to understanding the evolution of the nervous system on a large phylogenetic scale is the identification of homologous neuronal types. Here, we focus this search on the sensory and motor neurons of bilaterians, exploiting their well-defined molecular signatures in vertebrates. Sensorimotor circuits in vertebrates are of two types: somatic (that sense the environment and respond by shaping bodily motions) and visceral (that sense the interior milieu and respond by regulating vital functions).

Brainstem respiratory oscillators develop independently of neuronal migration defects in the Wnt/PCP mouse mutant looptail.

The proper development and maturation of neuronal circuits require precise migration of component neurons from their birthplace (germinal zone) to their final positions. Little is known about the effects of aberrant neuronal position on the functioning of organized neuronal groups, especially in mammals. Here, we investigated the formation and properties of brainstem respiratory neurons in looptail (Lp) mutant mice in which facial motor neurons closely apposed to some respiratory neurons fail to migrate due to loss of function of the Wnt/Planar Cell Polarity (PCP) protein Vangl2.

Breathing without CO(2) chemosensitivity in conditional Phox2b mutants.

Breathing is a spontaneous, rhythmic motor behavior critical for maintaining O(2), CO(2), and pH homeostasis. In mammals, it is generated by a neuronal network in the lower brainstem, the respiratory rhythm generator (Feldman et al., 2003).

Prenatal development of central rhythm generation.

Foetal breathing in mice results from prenatal activity of the two coupled hindbrain oscillators considered to be responsible for respiratory rhythm generation after birth: the pre-Bötzinger complex (preBötC) is active shortly before the onset of foetal breathing; the parafacial respiratory group (e-pF in embryo) starts activity one day earlier. Transcription factors have been identified that are essential to specify neural progenitors and lineages forming each of these oscillators during early development of the neural tube: Hoxa1, Egr2 (Krox20), Phox2b, Lbx1 and Atoh1 for the e-pF; Dbx1 and Evx1 for the preBötC which eventually grow contralateral axons requiring expression of Robo3. Inactivation of the genes encoding these factors leads to mis-specification of these neurons and distinct breathing abnormalities: apneic patterns and loss of central chemosensitivity for the e-pF (central congenital hypoventilation syndrome, CCHS, in humans), complete loss of breathing for the preBötC, right-left desynchronized breathing in Robo3 mutants.

Clonal analysis by distinct viral vectors identifies bona fide neural stem cells in the adult zebrafish telencephalon and characterizes their division properties and fate.

Neurogenesis is widespread in the zebrafish adult brain through the maintenance of active germinal niches. To characterize which progenitor properties correlate with this extensive neurogenic potential, we set up a method that allows progenitor cell transduction and tracing in the adult zebrafish brain using GFP-encoding retro- and lentiviruses. The telencephalic germinal zone of the zebrafish comprises quiescent radial glial progenitors and actively dividing neuroblasts.

Phox2b, congenital central hypoventilation syndrome and the control of respiration.

Neural networks in the hindbrain generate the pattern of motor activity that sustains breathing in mammals. Over the last years, increasing knowledge of the development and the molecular signatures of different classes of hindbrain neurons has led to a better definition of the neuronal circuits essential for adequate breathing. Here, we review how, on the basis of earlier clinical and genetic studies of a human respiratory disease, evidence from neurophysiology and mouse genetics has led to the conclusion that a restricted number of neuronal types expressing and depending on the Phox2b transcription factor play crucial roles in the control of respiration.

Hindbrain interneurons and axon guidance signaling critical for breathing.

Breathing is a bilaterally synchronous behavior that relies on a respiratory rhythm generator located in the brainstem. An essential component of this generator is the preBötzinger complex (preBötC), which paces inspirations. Little is known about the developmental origin of the interneuronal populations forming the preBötC oscillator network.

Teashirt 3 regulates development of neurons involved in both respiratory rhythm and airflow control.

Neonatal breathing in mammals involves multiple neuronal circuits, but its genetic basis remains unclear. Mice deficient for the zinc finger protein Teashirt 3 (TSHZ3) fail to breathe and die at birth. Tshz3 is expressed in multiple areas of the brainstem involved in respiration, including the pre-Bötzinger complex (preBötC), the embryonic parafacial respiratory group (e-pF), and cranial motoneurons that control the upper airways.