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J Appl Physiol 92: 826-834, 2002. First published October 5, 2001; doi:10.1152/japplphysiol.00839.2001
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Vol. 92, Issue 2, 826-834, February 2002

Paraventricular oxytocin neurons are involved in neural modulation of breathing

S. O. Mack1, P. Kc1, M. Wu1, B. R. Coleman1, F. P. Tolentino-Silva2, and M. A. Haxhiu1,2

1 Department of Physiology and Biophysics, Howard University, Washington, District of Columbia 20059; and 2 Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44106

In this study, we determined the projections of oxytocin-containing neurons of the paraventricular nucleus (PVN) to phrenic nuclei and to the rostral ventrolateral medullary (RVLM) region, which is known to be involved in respiratory rhythm generation. Studies were also designed to determine oxytocin-receptor expression within the RVLM and the physiological effects of their activation on respiratory drive and arterial blood pressure. Oxytocin immunohistochemistry combined with cholera toxin B, a retrograde tracer, showed that a subpopulation of oxytocin-containing parvocellular neurons in the dorsal and medial ventral regions of the PVN projects to phrenic nuclei. Similarly, a subpopulation of pseudorabies virus-labeled neurons in the PVN coexpressed oxytocin after injection of pseudorabies virus, a transynaptic retrograde marker, into the costal region of the diaphragm. A subpopulation of oxytocin expressing neurons was also found to project to the RVLM. Activation of this site by microinjection of oxytocin into the RVLM (0.2 nmol/200 nl) significantly increased diaphragm electromyographic activity and frequency discharge (P < 0.05). In addition, oxytocin increased blood pressure and heart rate (P < 0.05). These data indicate that oxytocin participates in the regulation of respiratory and cardiovascular activity, partly via projections to the RVLM and phrenic nuclei.

pre-Bötzinger complex; spinal cord; phrenic nuclei; oxytocin receptor; neurokinin-1 receptor; cholera toxin B subunit; pseudorabies virus


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