Activating convergent signal pathways in respiratory neurons of the ventral medullary group

Ponimaskin E, Manzke T, Lalley PM, Haller M, Guenther U, Bischoff AM, Bickmeyer U, Richter DW, Wilken B
2001 Respiratory Research  
1. Martin-Caraballo M, Greer JJ: Electrophysiological properties of rat phrenic motoneurons during the perinatal development. J Neurophysiol 1999, 81:1365-1378 2. Greer JJ, Allan DW, Martin-Caraballo M, Lemke RP: Invited Review: An overview of phrenic nerve and diaphragm muscle development in the perinatal rat. J Appl Physiol 1999, 86:779-786 3. Martin-Caraballo M, Campagnaro PA, Gao Y, Greer JJ: Contractile properties of the rat diaphragm during the perinatal period. J Appl Physiol 2000,
more » ... Physiol 2000, 88:573-580 4. Martin-Caraballo M, Greer JJ: Development of potassium conductances in perinatal rat phrenic motoneurons. J Neurophysiol 2000, 83:3497-3508 5. Martin-Caraballo M, Greer JJ: Voltage-sensitive calcium currents and their role in regulating phrenic motoneuron electrical excitability during the perinatal period. J Neurobiol 2001, 46:231-248 Acknowledgements: Funded by CIHR, AHFMR and Alberta Lung Association. Available online http://respiratory-research.com/content/2/S1 S4 control of breathing, characterized by depressed and irregular ventilation and central respiratory output and a lack of hypoxic ventilatory drive [1,2]. These deficits are due at least in part to loss of peripheral chemoafferent neurons that require BDNF for survival during fetal development [1,3,4]. Surprisingly, null mutations in the gdnf gene result in a similar phenotype, despite the fact that BDNF and GDNF are structurally unrelated and signal through wholly different classes of receptors. However, we recently found that BDNF and GDNF are both required for survival of the same population of chemoafferent neurons and that null mutations in either gene results in chemoafferent cell loss [5]. This dual requirement for BDNF and GDNF appears to be related to the fact that both molecules are expressed in the fetal carotid body and act as targetderived survival factors for chemoafferent neurons [5,6]. Loss of chemoafferent input at fetal stages is particularly deleterious for maturation of ventilatory function, as chemoafferent drive is required for stabilization of central respiratory output after birth. Potential implications of these findings for human developmental disorders of breathing will be discussed. References 1. Erickson JT, Conover JC, Borday V, Champagnat J, Barbacid M, Yancopoulos GD, Katz DM: Mice lacking brain-derived neurotrophic factor exhibit visceral sensory neuron losses distinct from mice lacking NT4 and display a severe developmental deficit in control of breathing. J Neurosci 1996, 16:5361-5371 2. Balkowiec A, Katz DM: Brain-derived neurotrophic factor is required for normal development of the central respiratory rhythm in mice. J Physiol 1998, 510:527-533 3. Hertzberg TH, Erickson JT, Fan G, Finley JCW, Katz DM: BDNF supports mammalian chemoafferent neurons in vitro and following peripheral target removal in vivo. Dev Biol 1994, 166:801-811 4. Conover JC, Katz DM, Erickson JT, Bianchi LM, Poueymirou WT, McClain J, Pan L, Helgren M, Ip NY, Boland P, et al.: Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature 1995, 375:235-238 5. Brady R, Zaidi IAS, Mayer C, Katz DM: BDNF is a target-derived survival factor for arterial baroreceptor and chemoafferent primary sensory neurons. J Neurosci 1999, 19:2131-2142 6. Erickson JT, Brosenitsch T, Katz DM: Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor are required simultaneously for survival of dopaminergic primary sensory neurons in vivo. J Neurosci 2001, 21:581-589 Acknowledgement: Supported by USPHS grants (NHLBI) to DMK.
doi:10.1186/rr109 doaj:20df73a270a94d1182bc8cd79a0759b2 fatcat:ldblmj6k6fgedf2ge22u4bxmoi