Sebastien Zanella

Sebastien Zanella
French National Centre for Scientific Research | CNRS · Institut de Neurosciences de la Timone

PhD

About

37
Publications
5,870
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2,715
Citations
Additional affiliations
September 2013 - present
French National Centre for Scientific Research
Position
  • PostDoc Position
January 2011 - August 2013
Aix-Marseille University
Position
  • PostDoc Position
January 2009 - December 2010
Seattle Children’s Research Institute
Position
  • PostDoc Position

Publications

Publications (37)
Article
Full-text available
Neuronal networks are endogenously modulated by aminergic and peptidergic substances. These modulatory processes are critical for maintaining normal activity and adapting networks to changes in metabolic, behavioral, and environmental conditions. However, disturbances in neuromodulation have also been associated with pathologies. Using whole animal...
Article
Full-text available
Phox2b-expressing glutamatergic neurons of the retrotrapezoid nucleus (RTN) display properties expected of central respiratory chemoreceptors; they are directly activated by CO2/H(+) via an unidentified pH-sensitive background K(+) channel and, in turn, facilitate brainstem networks that control breathing. Here, we used a knock-out mouse model to e...
Article
Full-text available
P/Q-type voltage-gated calcium channels (Ca(v)2.1) play critical presynaptic and postsynaptic roles throughout the nervous system and have been implicated in a variety of neurological disorders. Here we report that mice with a genetic ablation of the Ca(v)2.1 pore-forming α(1A) subunit (α(1A)(-/-)) encoded by CACNA1a (Jun et al., 1999) suffer durin...
Article
Full-text available
Leigh syndrome (LS) is a subacute necrotizing encephalomyelopathy with gliosis in several brain regions that usually results in infantile death. Loss of murine Ndufs4, which encodes NADH dehydrogenase (ubiquinone) iron-sulfur protein 4, results in compromised activity of mitochondrial complex I as well as progressive neurodegenerative and behaviora...
Article
Full-text available
Persistent sodium current (INaP) in the spinal locomotor network promotes two distinct nonlinear firing patterns: a self-sustained spiking triggered by a brief excitation in bistable motoneurons and bursting oscillations in interneurons of the central pattern generator (CPG). Here, we identify the NaV channels responsible for INaP and their role in...
Preprint
Full-text available
Persistent sodium current (INaP) in the spinal locomotor network promotes two distinct nonlinear firing patterns: a self-sustained spiking triggered by a brief excitation in bistable motoneurons and bursting oscillations in interneurons of the central pattern generator (CPG). Here, we identified the NaV channels responsible for INaP and their role...
Article
Full-text available
Chronic intermittent hypoxia (CIH) is a common state experienced in several breathing disorders, including obstructive sleep apnea (OSA) and apneas of prematurity. Unraveling how CIH affects the CNS, and in turn how the CNS contributes to apneas is perhaps the most challenging task. The preBötzinger complex (preBötC) is a pre-motor respiratory netw...
Article
Full-text available
In the cochlea, K+ is essential for mechano-electrical transduction. Here, we explore cochlear structure and function in mice lacking K+ channels of the two-pore domain family. A profound deafness associated with a decrease in endocochlear potential is found in adult Kcnk5−/− mice. Hearing occurs around postnatal day 19 (P19), and completely disapp...
Article
Full-text available
Key points Prostaglandin E 2 (PGE 2 ) augments distinct inspiratory motor patterns, generated within the preBötzinger complex (preBötC), in a dose‐dependent way. The frequency of sighs and gasping are stimulated at low concentrations, while the frequency of eupnoea increases only at high concentrations. We used in vivo microinjections into the preB...
Article
Phox2b‐expressing neurons of the retrotrapezoid nucleus (RTN) function as central respiratory chemoreceptors; they are directly activated by CO 2 /H ⁺ , via an unidentified pH‐sensitive background K ⁺ channel, to drive breathing. Here, we test the effect of TASK2 (K2P5, an alkaline‐activated background K ⁺ channel) channel deletion on the pH sensit...
Article
Full-text available
Cell type-specific expression of optogenetic molecules allows temporally precise manipulation of targeted neuronal activity. Here we present a toolbox of four knock-in mouse lines engineered for strong, Cre-dependent expression of channelrhodopsins ChR2-tdTomato and ChR2-EYFP, halorhodopsin eNpHR3.0 and archaerhodopsin Arch-ER2. All four transgenes...
Article
Breathing emerges through complex network interactions involving neurons distributed throughout the nervous system. The respiratory rhythm generating network is composed of micro networks functioning within larger networks to generate distinct rhythms and patterns that characterize breathing. The pre-Bötzinger complex, a rhythm generating network l...
Article
Full-text available
Breathing is controlled by a distributed network involving areas in the neocortex, cerebellum, pons, medulla, spinal cord, and various other subcortical regions. However, only one area seems to be essential and sufficient for generating the respiratory rhythm: the preBötzinger complex (preBötC). Lesioning this area abolishes breathing and following...
Article
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Neurons depend on aerobic metabolism, yet are very sensitive to oxidative stress and, as a consequence, typically operate in a low O(2) environment. The balance between blood flow and metabolic activity, both of which can vary spatially and dynamically, suggests that local O(2) availability markedly influences network output. Yet the understanding...
Article
N-Methyl-D-aspartate (NMDA) receptors have been implicated in epileptogenesis, but how these receptors contribute to epilepsy remains unknown. In particular, their role is likely to be complicated because of their voltage-dependent behavior. Here, the authors investigate how activation of NMDA receptors can affect the intrinsic production of oscill...
Article
Full-text available
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 parafaci...
Article
Rett syndrome is a neurodevelopmental disease accompanied by complex, disabling symptoms, including breathing symptoms. Because Rett syndrome is caused by mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2), Mecp2-deficient mice have been generated as experimental model. Males of Mecp2-deficient mice (Mecp2(-/y)) breathe...
Article
Prader-Willi syndrome (PWS) is a multigenic disorder caused by the loss of paternal expression of genes in the 15q11-q13 region. It is a complex and progressive disease. From birth, patients present breathing disorders (apnea, rhythm instability, hypoventilation and blunted response to changes in CO(2) or O(2)). Recent advances allowing early diagn...
Article
Rett syndrome (RTT) is a rare neurodevelopmental disease caused by mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2) and accompanied by complex symptoms, including erratic breathing and life-threatening apnoeas. In Mecp2-deficient male mice (Mecp2(-/y)), breathing is normal at birth but becomes altered after postnatal...
Article
The role of neuronal O 2 sensitivity in the preBötzinger complex (preBötC) is best demonstrated by network reconfiguration from fictive eupnea to gasping during hypoxic exposure. Here we demonstrate that the preBötC responds to relative rather than absolute changes in O 2 , and that the pattern of O 2 exposure (sustained versus intermittent) can al...
Article
In newborn mice of the control [C3H/HeJ (C3H)] and monoamine oxidase A-deficient (Tg8) strains, in which levels of endogenous serotonin (5-HT) were drastically increased, we investigated how 5-HT system dysregulation affected the maturation of phrenic motoneurons (PhMns), which innervate the diaphragm. First, using immunocytochemistry and confocal...
Article
Apneas are common and prognostically relevant disorders of the central control of breathing, but pharmacological interventions are dissatisfying. The respiratory phenotype of C57BL/6J mice is characterized by the occurrence of spontaneous central apneas with laryngeal closure. In the present study we investigated the impact of the 5-HT(1A) receptor...
Article
Full-text available
Prader-Willi syndrome is a neurogenetic disease resulting from the absence of paternal expression of several imprinted genes, including NECDIN. Prader-Willi children and adults have severe breathing defects with irregular rhythm, frequent sleep apneas, and blunted respiratory regulations. For the first time, we show that Prader-Willi infants have s...
Article
Prader-Willi Syndrome (PWS) is a complex neurogenetic disease with various symptoms, including breathing deficits and possible alteration of serotonin (5HT) metabolism. As PWS results from the absence of paternal expression of several imprinted genes among which NECDIN (Ndn), we examined whether Ndn deficiency in mice induced breathing and 5HT defi...
Article
Full-text available
Rett syndrome is a neurodevelopmental disease due to Mecp2 gene mutations that is associated to complex neurological symptoms, with bioaminergic deficits and life-threatening apneas related to sudden and unexpected death. In male mice, Mecp2-deficiency similarly induces medullary bioaminergic deficits, severe apneas and short life span. Here, we sh...
Article
Despite the clinical significance of central apneas in a wide range of disorders little is known about their pathogenesis. Research in this field has been hindered by the lack of appropriate animal models. Our goal was to determine whether the C57BL/6J mouse strain, which has an inherited predisposition for dysrhythmic breathing, exhibits spontaneo...
Article
The respiratory rhythm generator (RRG) is modulated by several endogenous substances, including acetylcholine (ACh) and noradrenaline (NA) that interact in several modulatory processes. To know whether ACh and NA interacted to modulate the RRG activity, we used medullary "en bloc" and slice preparations from neonatal mice where the RRG has been sho...
Article
Although compelling evidence exist that the respiratory rhythm generator is modulated by endogenous noradrenaline released from pontine A5 and A6 neurones, we examined whether medullary catecholaminergic neurones also participated in respiratory rhythm modulation. Experiments were performed in neonatal (postnatal days 0-6, P0-P6) and young mice (P1...
Article
Full-text available
Rett syndrome is a severe X-linked neurological disorder in which most patients have mutations in the methyl-CpG binding protein 2 (MECP2) gene and suffer from bioaminergic deficiencies and life-threatening breathing disturbances. We used in vivo plethysmography, in vitro electrophysiology, neuropharmacology, immunohistochemistry, and biochemistry...
Article
The survival of neonatal mammals requires a correct function of the respiratory rhythm generator (RRG), and therefore, the processes that control its prenatal maturation are of vital importance. In humans, lambs and rodents, foetal breathing movements (FBMs) occur early during gestation, are episodic, sensitive to bioamines, central hypoxia and inp...

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