There is increasing evidence that an essential component of the rhythm generating circuitry is located within a discrete region of the ventrolateral medulla termed the preB6tzinger complex. Nevertheless, an understanding of the preB6tzinger contribution to breathing awaits a comprehensive description of the pertinent properties and network interactions of the constituent neurons. The goal of this project to provide a reasonably complete description of the respiratory neuron types present in the preB6tzinger complex, including their discharge patterns, response to activation of selected afferent inputs, neurotransmitter (GABA, glutamate, glycine) content and pattern of synaptic connections formed with other preB6tzinger neurons. Given the small size of the preB6tzinger complex (in the adult rat it is approximately 0.6 mm long and about 1.5 mm in diameter, including dendrites), it is within our means to provide this analysis.
Three Specific Aims will be undertaken.
In Aim l, intracellular or extracellular recording will be used to classify neurons with respect to discharge pattern and their response to stimulation of vagus and superior laryngeal nerve afferents. The recorded neurons will then be injected with dye. Subsequent immunohistochemical analysis at the light and ultrastructural levels will identify the neurotransmitter content (GABA, glycine, glutamate) and their axonal projection patterns.
In Aim 2, synaptic interactions between preB6tzinger neurons will be identified with complementary electrophysiological and anatomical approaches. In the electrophysiological approach, either spike triggered averaging or cross-correlation approaches will be used with paired neuronal recordings. In anatomical experiments intra- or juxtacellular labeling will be used to dye-label cells in 2 different functional groups for subsequent light and ultrastructural analysis of their synaptic interactions.
In Aim 3, we will develop a detailed computational model of the preB6tzinger respiratory network using the identified neuronal properties and connectivity. The hypothesis to be addressed is that the neuronal types and synaptic interactions within the preB6tzinger complex are sufficient for respiratory rhythm generation in vivo.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL072415-05
Application #
7174301
Study Section
Special Emphasis Panel (ZRG1-SSS-3 (03))
Program Officer
Twery, Michael
Project Start
2003-01-01
Project End
2008-12-31
Budget Start
2007-01-01
Budget End
2008-12-31
Support Year
5
Fiscal Year
2007
Total Cost
$333,617
Indirect Cost
Name
Northwestern University at Chicago
Department
Physiology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Alheid, George F; McCrimmon, Donald R (2008) The chemical neuroanatomy of breathing. Respir Physiol Neurobiol 164:3-11
Kubin, Leszek; Alheid, George F; Zuperku, Edward J et al. (2006) Central pathways of pulmonary and lower airway vagal afferents. J Appl Physiol 101:618-27
Rybak, Ilya A; Stecina, Katinka; Shevtsova, Natalia A et al. (2006) Modelling spinal circuitry involved in locomotor pattern generation: insights from the effects of afferent stimulation. J Physiol 577:641-58
Rybak, Ilya A; Shevtsova, Natalia A; Lafreniere-Roula, Myriam et al. (2006) Modelling spinal circuitry involved in locomotor pattern generation: insights from deletions during fictive locomotion. J Physiol 577:617-39
Ptak, Krzysztof; Zummo, Greer G; Alheid, George F et al. (2005) Sodium currents in medullary neurons isolated from the pre-Botzinger complex region. J Neurosci 25:5159-70
Potts, Jeffrey T; Rybak, Ilya A; Paton, Julian F R (2005) Respiratory rhythm entrainment by somatic afferent stimulation. J Neurosci 25:1965-78
Jiang, Mingchen; Alheid, George F; Calandriello, Tara et al. (2004) Parabrachial-lateral pontine neurons link nociception and breathing. Respir Physiol Neurobiol 143:215-33
Alheid, George F; Milsom, William K; McCrimmon, Donald R (2004) Pontine influences on breathing: an overview. Respir Physiol Neurobiol 143:105-14
McCrimmon, Donald R; Alheid, George F; Jiang, Minchun et al. (2004) Converging functional and anatomical evidence for novel brainstem respiratory compartments in the rat. Adv Exp Med Biol 551:101-5
Rybak, Ilya A; Shevtsova, Natalia A; Paton, Julian F R et al. (2004) Modelling respiratory rhythmogenesis: focus on phase switching mechanisms. Adv Exp Med Biol 551:189-94

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