The long term goal of this research program is to understand the cellular and synaptic mechanisms involved in generating and controlling the mammalian respiratory rhythm. Clearly, breathing is essential to the maintenance of life itself, therefore, understanding the origin and regulation of the respiratory rhythm is of fundamental physiological importance. The respiratory rhythm is generated and controlled by a neuronal circuit within the brainstem but the mechanisms responsible for this rhythm have remained a mystery. Respiratory neurons are concentrated in two groups within the medulla. These groups are called the dorsal respiratory group (DRG) and the ventral respiratory group (VRG). This proposal is a competitive renewal for a project using an in vitro brainstem slice preparation to characterize the cellular and morphological properties of medullary respiratory neurons within these groups. During the previous grant period we refined the brainstem slice preparation and have exploited it to study the properties of neurons in the DRG. The cellular properties of neurons in the VRG, which is the largest group of respiratory neurons in the medulla, are virtually unknown. The VRG extends from the rostral reaches of the spinal cord to the ponto-medullary border and encompasses the nucleus ambiguus and retroambiguus as well as Botzinger's complex.
Our specific aims are: 1. To characterize the eloctrophysiological properties of neurons within the VRG using intracellular recording to quantify intrinsic cellular properties and to determine if classes of neurons can be defined by these properties. 2. To characterize the morphological properties of neurons in the VRG by intracellular staining with Lucifer yellow or horseradish peroxidase (HRP). 3. Are the properties of VRG neurons modified by neurotransmitters known to influence respiration? Candidate neurotransmitters include thyrotropin- releasing hormone, serotonin, and substance P. 4. To use dual intracellular recording to quantify synaptic interactions between DRG and VRG neurons.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL032336-04
Application #
3343702
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1984-01-01
Project End
1991-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Cleland, C L; Getting, P A (1993) Respiratory-modulated and phrenic afferent-driven neurons in the cervical spinal cord (C4-C6) of the fluorocarbon-perfused guinea pig. Exp Brain Res 93:307-11
Johnson, S M; Getting, P A (1992) Excitatory effects of thyrotropin-releasing hormone on neurons within the nucleus ambiguus of adult guinea pigs. Brain Res 590:1-5
Johnson, S M; Getting, P A (1991) Electrophysiological properties of neurons within the nucleus ambiguus of adult guinea pigs. J Neurophysiol 66:744-61
Haddad, G G; Donnelly, D F; Getting, P A (1990) Biophysical properties of hypoglossal neurons in vitro: intracellular studies in adult and neonatal rats. J Appl Physiol 69:1509-17
Richerson, G B; Getting, P A (1990) Preservation of integrative function in a perfused guinea pig brain. Brain Res 517:7-18
Haddad, G G; Getting, P A (1989) Repetitive firing properties of neurons in the ventral region of nucleus tractus solitarius. In vitro studies in adult and neonatal rat. J Neurophysiol 62:1213-24
Getting, P A (1989) Emerging principles governing the operation of neural networks. Annu Rev Neurosci 12:185-204
Johnson, S M; Getting, P A (1988) Phrenic motor nucleus of the guinea pig: dendrites are bundled without clustering of cell somas. Exp Neurol 101:208-20
Dekin, M S; Getting, P A (1987) In vitro characterization of neurons in the ventral part of the nucleus tractus solitarius. II. Ionic basis for repetitive firing patterns. J Neurophysiol 58:215-29
Dekin, M S; Getting, P A; Johnson, S M (1987) In vitro characterization of neurons in the ventral part of the nucleus tractus solitarius. I. Identification of neuronal types and repetitive firing properties. J Neurophysiol 58:195-214

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