The purpose of the research in this proposal is to investigate hypothalamic involvement in the control of the respiratory system. Several studies have demonstrated that areas in the hypothalamus are involved in modulating some cardiovascular reflexes. For example, the cardiovascular responses to stimulation of baroreceptors and peripheral chemoreceptors are known to be modified by sites in the hypothalamus. Even though activation of these receptors also affects ventilation, almost no research has examined a role of the hypothalamus in regulating respiratory responses. Therefore, the specific aims of the studies described in this proposal are to investigate a potential role of hypothalamic sites in regulating respiratory reflexes and to determine the neurotransmitters utilized by the hypothalamic sites which modulate breathing. The respiratory reflexes to be studied are those evoked by stimulation of 1) pulmonary stretch receptors (Hering-Breuer reflex); 2) peripheral chemoreceptors; 3) central chemoreceptors and 4) arterial baroreceptors. Three sets of experiments will be performed in anesthetized cats. First, the effects of changing the """"""""excitability state"""""""" of neurons in selected hypothalamic sites upon the respiratory reflexes will be determined. The excitability state will be raised by chemical or electrical stimulation and will be lowered by electrolytic lesions or by focal cooling of hypothalamic sites. In a second set of experiments the effects upon the respiratory reflexes of microinjecting neurotransmitter antogonists into the hypothalamus will be evaluated. Finally, it will be determined if the respiratory stimuli listed above alter the discharge frequency of hypothalamic neurons. The information gained from these experiments should add to the overall understanding of the neural control of respiration. These findings may offer insights into the neurological abnormalities responsible for some central respiratory disorders.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Respiratory and Applied Physiology Study Section (RAP)
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University of Illinois Urbana-Champaign
Schools of Arts and Sciences
United States
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Ichiyama, Ronaldo M; Waldrop, Tony G; Iwamoto, Gary A (2004) Neurons in and near insular cortex are responsive to muscular contraction and have sympathetic and/or cardiac-related discharge. Brain Res 1008:273-7
Kramer, J M; Waldrop, T G (1998) Neural control of the cardiovascular system during exercise. An integrative role for the vestibular system. J Vestib Res 8:71-80
Horn, E M; Waldrop, T G (1997) Oxygen-sensing neurons in the caudal hypothalamus and their role in cardiorespiratory control. Respir Physiol 110:219-28
Iwamoto, G A; Waldrop, T G (1996) Lateral tegmental field neurons sensitive to muscular contraction: a role in pressor reflexes? Brain Res Bull 41:111-20
Nolan, P C; Waldrop, T G (1996) Ventrolateral medullary neurons show age-dependent depolarizations to hypoxia in vitro. Brain Res Dev Brain Res 91:111-20
Iwamoto, G A; Wappel, S M; Fox, G M et al. (1996) Identification of diencephalic and brainstem cardiorespiratory areas activated during exercise. Brain Res 726:109-22
Ryan, J W; Waldrop, T G (1995) Hypoxia sensitive neurons in the caudal hypothalamus project to the periaqueductal gray. Respir Physiol 100:185-94
Nolan, P C; Dillon, G H; Waldrop, T G (1995) Central hypoxic chemoreceptors in the ventrolateral medulla and caudal hypothalamus. Adv Exp Med Biol 393:261-6
Shonis, C A; Waldrop, T G (1995) In vitro effects of GABA and hypoxia on posterior hypothalamic neurons from spontaneously hypertensive and Wistar-Kyoto rats. Brain Res Bull 36:461-6
Horn, E M; Waldrop, T G (1994) Modulation of the respiratory responses to hypoxia and hypercapnia by synaptic input onto caudal hypothalamic neurons. Brain Res 664:25-33

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