Cardiovascular function is regulated, in part, by neuronal signaling through oligosynaptic pathways in the brainstem. The synaptic and intrinsic electrical properties of the neurons in these brainstem pathways and how they respond to external stimuli combine to generate an appropriate neuronal output and hence neural regulation of blood pressure and heart rate. Our research is aimed at understanding how these neurons are regulated in normal conditions and how they are altered during pathophysiological conditions such as hypertension and in other states in which neural control of the cardiovascular system is altered, such as occurs with Parkinson's disease, diabetes, depression, and exposure to environmental pollutants. Characterizing the intrinsic and synaptic properties of these neurons and how these properties are regulated can provide potential new drug targets in regulating cardiovascular function.

A second related research interest is aimed at neural regulation of respiration and lung function. Release of inflammatory mediators in the lungs and airways promotes local inflammatory responses, which in turn trigger synaptic and intrinsic changes in brainstem neurons regulating cough and lung function through CNS reflex pathways. Using electrophysiological and molecular biological approaches, we hope to understand how the changes in the phenotype and behavior of these neurons trigger increases in cough and breathing pattern in response to environmental stimuli.

Selected Publications

Liu Z, Chen CY, Bonham AC. Frequency limits on aortic baroreceptor input to nucleus tractus solitarii. Am J Physiol Heart Circ Physiol. 2000 Feb;278(2):H577-85. Abstract.

Mutoh T, Joad JP, Bonham AC. Chronic passive cigarette smoke exposure augments bronchopulmonary C-fibre inputs to nucleus tractus solitarii neurones and reflex output in young guinea-pigs. J Physiol. 2000 Feb 15;523 Pt 1:223-33.Abstract.

Mutoh T, Bonham AC, Joad JP. Substance P in the nucleus of the solitary tract augments bronchopulmonary C fiber reflex output. Am J Physiol Regul Integr Comp Physiol. 2000 Oct;279(4):R1215-23. Abstract.

Bonham AC, Chen CY, Mutoh T, Joad JP. Lung C-fiber CNS reflex: role in the respiratory consequences of extended environmental tobacco smoke exposure in young guinea pigs. Environ Health Perspect. 2001 Aug;109 Suppl 4:573-8. Abstract.

Chen CY, Bonham AC, Schelegle ES, Gershwin LJ, Plopper CG, Joad JP. Extended allergen exposure in asthmatic monkeys induces neuroplasticity in nucleus tractus solitarius. J Allergy Clin Immunol. 2001 Oct;108(4):557-62. Abstract.

Chen CY, Ling Eh EH, Horowitz JM, Bonham AC. Synaptic transmission in nucleus tractus solitarius is depressed by Group II and III but not Group I presynaptic metabotropic glutamate receptors in rats. J Physiol. 2002 Feb 1;538(Pt 3):773-86. Abstract.

Kajekar R, Chen CY, Mutoh T, Bonham AC. GABA(A) receptor activation at medullary sympathetic neurons contributes to postexercise hypotension. Am J Physiol Heart Circ Physiol. 2002 May;282(5):H1615-24. Abstract.

Bonham AC, Chen CY. Glutamatergic neural transmission in the nucleus tractus solitarius: N-methyl-D-aspartate receptors. Clin Exp Pharmacol Physiol. 2002 May-Jun;29(5-6):497-502. Abstract.

Chen CY, Munch PA, Quail AW, Bonham AC. Postexercise hypotension in conscious SHR is attenuated by blockade of substance P receptors in NTS. Am J Physiol Heart Circ Physiol. 2002 Nov;283(5):H1856-62. Abstract.

Chen CY, Bonham AC, Plopper CG, Joad JP. Neuroplasticity in nucleus tractus solitarius neurons after episodic ozone exposure in infant primates. J Appl Physiol. 2003 Feb;94(2):819-27.Abstract.

Sekizawa SI, Joad JP, Bonham AC. Substance P presynaptically depresses transmission of sensory input to bronchopulmonary neurons in nucleus tractus solitarius. J Physiol. 2003 Oct 15;552(Pt 2):547-59. Abstract.

Joad JP, Munch PA, Bric JM, Evans SJ, Pinkerton KE, Chen CY, Bonham AC. Passive smoke effects on cough and airways in young guinea pigs: role of brainstem substance P. Am J Respir Crit Care Med. 2004 Feb 15;169(4):499-504. Abstract.

Chen CY, Bonham AC. Glumate suppresses GABA release via presynaptic metabotropic glumate receptors at baroreceptor neurones in rats. J Physiol. 2005 Jan 15:562(Pt 2):535-51. Abstract.

Bonham AC, Sekizawa SI, Joad JP. Plasticity of central mechanisms for cough. Pulm Pramacol Their. 2004;17(6):453-7; discussion 469-70. Review. Abstract.

Sekizawa S, Bonham AC. Group I metabotropic glutamate receptors on secod-order baroreceptor neurons are tonically activated and induce a Na+-Ca2+ exchange current. J Neurophysiol. 2006 Feb;95(2):882-92. Abstract.

Bonham AC, Chen CY, Sekizawa S, Joad JP. Plasticity in the nucleus tractus solitarius and its influence on lung and airway reflexes. J Appl Physiol. 2006 July; 101(1):322-7. Abstract.

Bonham AC, Sekizawa S, Chen CY, Joad JP. Plasticity of brainstem mechanisms of cough. Respir Physiol Neurobiol. 2006 Jul 28;152(3):312-9. Abstract.