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Gilles Fortin

Publications and source records attributed to Gilles Fortin.

16 recordsLinked to original sources
PubMed2006

Vesicular glutamate transporter 2 is required for central respiratory rhythm generation but not for locomotor central pattern generation.

Glutamatergic excitatory neurotransmission is dependent on glutamate release from presynaptic vesicles loaded by three members of the solute carrier family, Slc17a6-8, which function as vesicular glutamate transporters (VGLUTs). Here, we show that VGLUT2 (Slc17a6) is required for life ex utero. Vglut2 null mutant mice die immediately after birth because of the absence of respiratory behavior. Investigations at embryonic stages revealed that neural circuits in the location of the pre-Bötzinger (PBC) inspiratory rhythm generator failed to become active. However, neurons with bursting pacemaker properties and anatomical integrity of the PBC area were preserved. Vesicles at asymmetric synapses were fewer and malformed in the Vglut2 null mutant hindbrain, probably causing the complete disruption of AMPA/kainate receptor-mediated synaptic activity in mutant PBC cells. The functional deficit results from an inability of PBC neurons to achieve synchronous activation. In contrast to respiratory rhythm generation, the locomotor central pattern generator of Vglut2 null mutant mice displayed normal rhythmic and coordinated activity, suggesting differences in their operating principles. Hence, the present study identifies VGLUT2-mediated signaling as an obligatory component of the developing respiratory rhythm generator.

Animals↗
PubMed2005

Tuning of external-cavity semiconductor lasers with chirped diffraction gratings.

We present a novel scheme of tunable semiconductor laser based on the use of a chirped grating in an external cavity. The chirped grating is fabricated using a simple holographic technique: two Gaussian beams having wavefronts with different radii of curvature are brought to interfere on a photoresist layer. The tuning properties of chirped gratings have been investigated with semiconductor lasers operated with an external cavity. With this type of grating positioned in Littrow configuration, the wavelength selection can be done by translating the grating without any need to rotate it. This cavity configuration provides a tunable output beam with an angle of propagation that is independent of the wavelength. The translation of chirped gratings was shown to tune a visible diode laser and an infrared diode laser over the same spectral band as the conventional tuning scheme where an unchirped grating is rotated.

Journal Article↗
PubMed2005

Chirped holographic grating used as the dispersive element in an optical spectrometer.

We have developed a new design of optical spectrometer based on the use of a chirped holographic grating inscribed on a flat substrate. This type of grating has a surface modulation with a spatially varying period. The ability of the chirped grating to focus a beam is exploited to reduce significantly the physical dimensions of the instrument. Wavelength selection is achieved by a pure translation of the chirped grating. The properties of the chirped grating spectrometer have been characterized with different lasers and arc lamps and compared with those of two commercial spectrometers. A performance parameter has been defined, enabling the various instruments to be compared.

Journal Article↗
PubMed2005

Emergence of the pre-Bötzinger respiratory rhythm generator in the mouse embryo.

To obtain insights into the emergence of rhythmogenic circuits supporting respiration, we monitored spontaneous activities in isolated brainstem and medullary transverse slice preparations of mouse embryos, combining electrophysiological and calcium imaging techniques. At embryonic day 15 (E15), in a restricted region ventral to the nucleus ambiguus, we observed the onset of a sustained high-frequency (HF) respiratory-like activity in addition to a preexisting low-frequency activity having a distinct initiation site, spatial extension, and susceptibility to gap junction blockers. At the time of its onset, the HF generator starts to express the neurokinin 1 receptor, is connected bilaterally, requires active AMPA/kainate glutamatergic synapses, and is modulated by substance P and the mu-opioid agonist D-Ala2-N-Me-Phe4-Glycol5-enkephalin. We conclude that a rhythm generator sharing the properties of the neonatal pre-Bötzinger complex becomes active during E15 in mice.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2005

The work of Ambroise Tardieu: the first definitive description of child abuse.

The first important monograph describing the battered child syndrome was written in 1860 by Ambroise Tardieu, a French forensic physician. Here is a translation of his article, published in the Annales d'hygiene publique et de medecine legale, with the title "Etude medico-legale sur les sevices et mauvais traitements exerces sur des enfants." The first part of his article is entirely translated. A brief summary of the 32 cases report described by Tardieu in the second part of his article is presented.

Adolescent↗
PubMed2004

Induction of a parafacial rhythm generator by rhombomere 3 in the chick embryo.

Observations of knock-out mice suggest that breathing at birth requires correct development of a specific hindbrain territory corresponding to rhombomeres (r) 3 and 4. Focusing on this territory, we examined the development of a neuronal rhythm generator in the chick embryo. We show that rhythmic activity in r4 is inducible after developmental stage 10 through interaction with r3. Although the nature of this interaction remains obscure, we find that the expression of Krox20, a segmentation gene responsible for specifying r3 and r5, is sufficient to endow other rhombomeres with the capacity to induce rhythmic activity in r4. Induction is robust, because it can be reproduced with r2 and r6 instead of r4 and with any hindbrain territory that normally expresses Krox20 (r3, r5) or can be forced to do so (r1, r4). Interestingly, the interaction between r4 and r3/r5 that results in rhythm production can only take place through the anterior border of r4, revealing a heretofore unsuspected polarity in individual rhombomeres. The r4 rhythm generator appears to be homologous to a murine respiratory parafacial neuronal system developing in r4 under the control of Krox20 and Hoxa1. These results identify a late role for Krox20 at the onset of neurogenesis.

Action Potentials↗
PubMed2003

Expression of functional tyrosine kinase B receptors by rhythmically active respiratory neurons in the pre-Bötzinger complex of neonatal mice.

Genetic loss of brain-derived neurotrophic factor (BDNF) severely disrupts brainstem control of respiratory rhythmogenesis in newborn mice; however, the sites at which BDNF acts to regulate respiratory rhythmogenesis are unknown. Using immunochemical and multiplex RT-PCR analysis in mouse brainstem slices, we report that the BDNF receptor, Tyrosine kinase B (TrkB), is strongly expressed in the pre-Bötzinger complex (PBC), the presumed site for rhythm generation, and colocalizes with neurokinin 1 (NK1), a marker of neurons critical for breathing. The period of the respiratory rhythm generated by PBC neurons in vitro was increased by 30% after BDNF treatment (100 ng/ml) and not by nerve growth factor (100 ng/ml) or BDNF (100 ng/ml) in the presence of the tyrosine kinase inhibitor K252a (200 nm). Both synaptic and voltage-dependent properties of PBC neurons were modified by BDNF. Synaptic currents underlying spontaneous rhythmic bursts and glutamate-evoked currents were enhanced by 66 and 33%, respectively. BDNF reduced the Ih current amplitude in rhythmic neurons by 46% and shifted its activation curve by -17 mV. All neurons expressing TrkB mRNA (n = 8) also expressed mRNAs for the Ih current [hyperpolarization-activated cyclic nucleotide-sensitive cation nonselective channel (HCN1)], and three of four NK1-positive neurons coexpressed TrkB and HCN mRNA. Six of 16 PBC neurons expressed BDNF mRNA, supporting the possibility of autocrine and paracrine actions of BDNF within the respiratory pattern generator. Our data demonstrate that BDNF can modulate respiratory network activity through TrkB signaling in rhythmic PBC neurons.

Animals↗
PubMed2003

Developmental molecular switches regulating breathing patterns in CNS.

The present paper presents some of the molecular switches that may operate at early embryonic stages to make development of the brainstem respiratory rhythm generator a robust and irreversible process. We concentrate on the role of transient Hox-related gene expression patterns in register with the regionalisation of the rhombencephalic neural tube along the antero-posterior axis. Using different recording and isolation procedures in chick embryos, we show that the hindbrain is subdivided at E1 into developmental units (rhombomeres) intrinsically able to produce rhythm generating neuronal circuits active at E5. At E6, intrinsic cues also allow a progressive maturation of episodic rhythm generators that persists after isolation of the hindbrain in vitro and requires odd/even rhombomeric interactions at E1. From these results and from respiratory pathologies observed in transgenic mice, we are beginning to understand that, despite diversity of breathing patterns and adaptations, there are links between developmental control genes and adult respiration.

Animals↗
PubMed2003

From hindbrain segmentation to breathing after birth: developmental patterning in rhombomeres 3 and 4.

Respiration is a rhythmic motor behavior that appears in the fetus and acquires a vital importance at birth. It is generated within central pattern-generating neuronal networks of the hindbrain. This region of the brain is of particular interest since it is the most understood part with respect to the cellular and molecular mechanisms that underlie its development. Hox paralogs and Hox-regulating genes kreisler/mafB and Krox20 are required for the normal formation of rhombomeres in vertebrate embryos. From studies of rhombomeres r3 and r4, the authors review mechanisms whereby these developmental genes may govern the early embryonic development of para-facial neuronal networks and specify patterns of motor activities operating throughout life. A model whereby the regional identity of progenitor cells can be abnormally specified in r3 and r4 after a mutation of these genes is proposed. Novel neuronal circuits may develop from some of these misspecified progenitors while others are eliminated, eventually affecting respiration and survival after birth.

Animals↗
PubMed2002

Early development of respiratory rhythm generation in mouse and chick.

We are investigating neuronal circuits resulting from conservative developmental mechanisms orchestrating the segmentation of the vertebrates hindbrain into compartments called rhombomeres (r). Segmentation transcription factors Hoxa1, Krox20 and kreisler are expressed in the future rhombomeres r4-r5, r3 and r5, r5-r6, respectively. In mice, the in vivo and in vitro analysis of neuronal groups after inactivation of these three genes revealed distinct postnatal respiratory phenotypes associated with defects of central respiratory controls resulting from deletion, neoformation or reconfiguration of modular circuits. In chick and mice, we have found neuronal rhythm generators that conform to the rhombomeric anatomical pattern as early as at the end of the segmentation. By isolating chick hindbrain segments in vitro, we have also identified rhombomeric motifs allowing the formation or deletion of a specific (GABAergic) rhythm-promoting module. Therefore, primordial rhombomeric organization of the hindbrain seems to determine a modular organization of the rhythmogenic network, thereby influencing later function of brainstem respiratory control networks.

Animals↗
PubMedDate not supplied

Developmental gene control of brainstem function: views from the embryo.

The respiratory rhythm is generated within the hindbrain reticular formation, rostrally in the vicinity of the facial nucleus and caudally within the vagal/glossopharyngeal domain. This is probably one of the best models to understand how genes have been selected and conserved to control adaptive behaviour in vertebrates. The para-facial region is well understood with respect to the transcription factors that underlie antero-posterior specification of neural progenitors in the embryo. Hox paralogs and Hox-regulating genes kreisler and Krox-20 govern transient formation of developmental compartments, the rhombomeres, in which rhythmic neuronal networks develop. Hox are master genes selecting and coordinating the developmental fate of reticular and motor neurons thereby specifying patterns of motor activities operating throughout life. Neuronal function and development are also tightly linked in the vagal/glossopharyngeal domain. At this level, bdnf acts as a neurotrophin of peripheral chemoafferent neural populations and as a neuromodulator of the central rhythmogenic respiratory circuits. A general view is now emerging on the role of developmental transcription and trophic factors allowing the coordinated integration of different neuronal types to produce, and eventually refine, respiratory rhythmic pattern in a use-dependent manner.

Animals↗