Biomedical subjects

Jean Champagnat

Publications and source records attributed to Jean Champagnat.

24 records · Page 2Linked to original sources

PubMed2002

Respiratory function in mice lacking or overexpressing the prion protein.

We investigated a possible involvement of the prion protein in ventilatory control in four groups of mice, those deficient for the prion protein (PrP(c)), those overexpressing the prion protein, and two groups of genetically and age-matched controls. Ventilatory patterns of unrestrained mice were measured in a whole-body plethysmograph. Between each genotype and its control, we compared ventilation at rest and the ventilatory response to moderate hypoxia (10-12% O2), hyperoxia and hyperoxic hypercapnia. Mice lacking or overexpressing PrP(c) and their respective controls showed similar ventilatory patterns at rest and similar chemosensory responses when awake and under urethane anesthesia. Our results do not support the view that PrP(c) may play any significant role in basal ventilation or in the chemosensory ventilatory control of adult mice.

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PubMed2002

Segment-specific expression of connexin31 in the embryonic hindbrain is regulated by Krox20.

Communication and interaction between cells has been shown to be important during the embryonic development of the vertebrate hindbrain, which becomes transiently subdivided into segments called rhombomeres (r). One gene family allowing intercellular communication and possibly being involved in the control of hindbrain development is the connexin family encoding gap junction channels. Here, we have characterized in detail the previously observed (Dahl et al., 1997) expression of one particular connexin gene, connexin31 (Cx31), in the mouse embryonic hindbrain and compared it with that of Cx43 and Cx36. We found transient Cx31 expression from approximately embryonic day (E) E8-E11 in two small lateral/dorsal subgroups of cells in the hindbrain. We could show that these spots of expression corresponded to r3 and r5 and that Cx31 expression in r3 and r5 was controlled by the transcription factor Krox20. In contrast, expression of Cx43 and Cx36 started later (from E9.5 and E10.5, respectively) and was confined to longitudinal stripes of expression. In addition, from E10.5-E11.5, Cx31 was expressed by a column of cells in ventral r4, most likely representing contralateral vestibulo-acoustic efferent neurons, immediately anterior to a ventral column expressing Cx36 at the same stage. From E11.5 onward, another site of Cx31 expression was detected in the boundary cap cells in the entry/exit points of all mixed sensory/motor and in the entry points of pure sensory nerves. This expression was not present in the boundary cap cells of the exit points of pure motor nerves. So far, our analysis of the hindbrain area of Cx31-deficient embryos in terms of projections of sensory or motor neurons or in the generation or migration of neurons has not yet revealed any obvious defects.

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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.

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PubMed2002

Different respiratory control systems are affected in homozygous and heterozygous kreisler mutant mice.

During embryonic development, restricted expression of the regulatory genes Krox20 and kreisler are involved in segmentation and antero-posterior patterning of the hindbrain neural tube. The analysis of transgenic mice in which specific rhombomeres (r) are eliminated points to an important role of segmentation in the generation of neuronal networks controlling vital rhythmic behaviours such as respiration. Thus, elimination of r3 and r5 in Krox20-/- mice suppresses a pontine antiapneic system (Jacquin et al., 1996). We now compare Krox20-/- to kreisler heterozygous (+/kr) and homozygous (kr/kr) mutant neonates. In +/kr mutant mice, we describe hyperactivity of the antiapneic system: analysis of rhythm generation in vitro revealed a pontine modification in keeping with abnormal cell specifications previously reported in r3 (Manzanares et al., 1999b). In kr/kr mice, elimination of r5 abolished all +/kr respiratory traits, suggesting that +/kr hyperactivity of the antiapneic system is mediated through r5-derived territories. Furthermore, collateral chemosensory pathways that normally mediate delayed responses to hypoxia and hyperoxia were not functional in kr/kr mice. We conclude that the pontine antiapneic system originates from r3r4, but not r5. A different rhythm-promoting system originates in r5 and kreisler controls the development of antiapneic and chemosensory signal transmission at this level.

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PubMed1998

Activity in sparsely connected excitatory neural networks: effect of connectivity.

The Nucleus Tractus Solitarius (NTS) of the brainstem contains a neural circuit with only excitatory connections displaying a spontaneous activity involved in the control of respiration. A model of a network with random connections is presented and is used to investigate a possible mechanism of spontaneous activity generation consisting of the amplification of a low-background activity by the excitatory connections. First, the steady states of the network model and its ability to amplify the activity are studied. Then, a low-background activity is introduced, and dynamics of simulated networks are examined. Low-tonic, slow-phasic and fast-tonic activities are successively observed when the mean number K of connections per neuron increases. The transition between the two first types of activity is progressive whereas the transition from slow-phasic to fast-tonic activity is sharp. Simulation results show that activities of low frequency can be obtained with the proposed mechanism of spontaneous activity generation only if the network connectivity is low.

Journal Article↗

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.

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