Project Details


In peripherally chemodenervated animals, exposure to hypoxia results in
phrenic neurogram depression followed by gasping, a respiratory pattern
which is thought to be important for quick reoxygenation following
remission of hypoxia. During eupnea, respiratory patterning is determined
by phase-specific inhibitory interactions between the neuronal components
of the respiratory pattern generator. The alterations of this circuit
which are the presumed bases of the effects of hypoxia on respiratory
patterning are unknown. The studies in this proposal seek to determine how
the interaction of respiratory neurons is modified during hypoxia with
resultant changes in respiratory patterning. The following hypotheses
will be tested: 1) Hypoxic respiratory depression results from alteration
of the balance between inhibitory and excitatory inputs to respiratory
neurons with GABAergic inhibition predominating. This hypothesis will be
tested by examining the response of respiratory neurons to iontophoretic
application of inhibitory neurotransmitter antagonists and glutamate
during eupnea and hypoxic depression; 2) The respiratory pattern
generation circuit during gasping is a reduced circuit consisting of
primarily inspiratory elements and few propriobulbar inhibitory or
expiratory elements. This hypothesis will be directly tested by
determining which populations of respiratory neurons are active during
gasping; 3) Inspiratory neurons are disinhibited during gasping. The
response of inspiratory neurons to the inhibitory neurotransmitter, gamma-
aminobutyric acid (GABA), will be tested during eupnea and gasping to
differentiate between potential pre- and postsynaptic mechanisms of
disinhibition during gasping; 4) Excitatory neurotransmission in the
respiratory pattern generator during gasping requires activation of
ionotropic glutamergic pathways. We will test this hypothesis by assessing
the response of respiratory neurons to ionotropic glutamergic antagonists
during eupnea and gasping. Taken together, these studies will permit
detailed evaluation of the changes in respiratory neuronal activity and
synaptic interactions which underlie the respiratory patterning changes
seen during hypoxia.
Effective start/end date4/1/963/31/00


  • National Heart, Lung, and Blood Institute


  • Pulmonary and Respiratory Medicine


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