Neurobiology and Circulatory Control Laboratory

Description

The Laboratory of Neurobiology is located in research buildings at the Iowa City Department of Veterans Affairs Medical Center. Over the past 20 years it has been funded by grants from the Department of Veterans Affairs, the American Heart Association, and the Heart, Lung and Blood Institute of the National Institutes of Health. The seminal focus of the laboratory is the study of central autonomic control as it relates to regulation of the cardiovascular system. The laboratory integrates physiological, pharmacological, neurochemical, immunohistochemical, microscopy (light, confocal and electron microscopy), and molecular/cellular techniques to study neurotransmitter systems that may mediate transmission of signals at central synapses in cardiovascular reflex pathways.

Projects

• Identification of the link between glutamate and nitric oxide in transmission of cardiovascular reflex signals in the brain stem. These studies test the hypothesis that glutamate transmission is critically linked to synthesis of nitric oxide by local cardiovascuneurons in the brain stem but that transduction of signals by ionotropic glutamate receptors differs from that by metabotropic receptors.
• Identification of the role played by preganglionic parasympathetic neurons of the pontine superior salivatory nucleus in cerebrovascular control. These studies have already established for the first time that arterial baroreflexes may modulate cerebral circulation through direct projections from the nucleus tractus solitarii, where baroreceptor nerves terminate, to the superior salivatory nucleus. We now seek to test the hypothesis that the baroreceptor projections to the pons use glutamate as an excitatory transmitter and to determine how this pathway participates in protecting the brain from damage caused by ischemia.
• Identification of the role played by the substance P receptor in cardiovascular reflex transmission by neurons in the nucleus tractus solitarii. We have shown that selective destruction of neurons that express the substance P receptor alters baroreflex transmission but also leads to cardiac changes and sudden death in some treated animals. The cardiac changes in these animals in many ways mirror those seen in humans after subarachnoid hemorrhage.
• In summary the projects have potentially important bearing on stroke, hypertension, and sudden death and could lead to novel therapies based on their pharmacological findings.

Recent Publications / Reviews
Victor, RG and Talman, WT. Comparative effects of clonidine and dihydroergotamine on venomotor tone and orthostatic tolerance in patients with severe hypoadrenergic orthostatic hypotension. Am. J. Med. 112: 361-368, 2002.

Talman, WT and Nitschke Dragon, D. Inhibiting the nucleus tractus solitarii extends cerebrovascular autoregulation during hypertension. Brain Res. 931:92-95, 2002.

Agassandian, K, Fazan, VPS, Adanina, V, and Talman, WT. Direct projections from the cardiovascular nucleus tractus solitarii to the superior salivatory nucleus: a link to cerebrovascular regulation. J. Comp. Neurol. 452:242-254, 2002.

Lin, L.H., Talman, W.T. Coexistence of NMDA and AMPA receptor subunits with nNOS in the nucleus tractus solitarii of rat. J. Chem. Neuroanat. 24:287-296, 2002.

Riley, J., Lin, L.H., Chianca, D.A.,Jr., Talman, W.T. NK1 receptors are critical in processing baroreflex signals in rat nucleus tractus solitarii. Hypertension. 40:823-826, 2002.

Bauman, NM, Deqiang, W., Luschei, ES and Talman, WT. The effect of substance P injection into the nucleus tractus solitarius of rats on laryngeal adductor activity and cardiovascular and respiratory systems. Ann. Otol. Rhinol. Laryngol. 111:875-883, 2002.

Lin, L.H., Agassandian, K., Fujiyama, F., Kaneko, T. and Talman, W.T. Evidence for glutamatergic input to pontine preganglionic neurons of the superior salivatory nucleus in rat. J. Chem. Neuroanat. 25:261-268, 2003.

Agassandian, K., Fazan, V.P.S., Margaryan, N., Nitschke Dragon, D., Riley, J., Talman, W.T. A Novel Central Pathway Links Arterial Baroreceptors and Pontine Parasympathetic Neurons in Cerebrovascular Control. Cell. Mol. Neurobiol. 23:463-479, 2003.

Talman, W.T. Glutamate and blood pressure in multiple system atrophy. (Editorial) Clin. Auton. Res. 13:239-241, 2003.

Lin, L.H., Edwards, R.H., Fremeau, R.T.J., Fujiyama, F., Kaneko, T., Talman, W.T. Vesicular Glutamate Transporter Colocalizes with Neuronal Nitric Oxide Synthase in Rat Nucleus Tractus Solitarii. Neuroscience. 123: 247-255, 2004.

Chianca, D.A., Jr., Lin, L.H., Nitschke Dragon, D., Talman, W.T. Glutamate Receptors in the Nucleus Tractus Solitarii are Linked to Soluble Guanylate Cyclase. Am. J. Physiol. Heart & Circ. Physiol. 286: H1521-1527, 2004.

Talman, W.T., Nitschke Dragon, D. Transmission of arterial baroreflex signals depends on neuronal nitric oxide synthase. Hypertension. 43:820-824, 2004.

Lin, L.H., Talman, W.T. Soluble guanylate cyclase and neuronal nitric oxide synthase colocalize in rat nucleus tractus solitarii. J.Chem.Neuroanat. 29:127-136, 2005.

Lin, L.H., Talman, W.T. Nitroxidergic neurons in rat nucleus tractus solitarii express vesicular glutamate transporter 3. J. Chem. Neuroanat. 29:179-191, 2005.

Lin, L.H., Talman, W.T. Vesicular glutamate transporters and neuronal nitric oxide synthase colocalize in aortic depressor afferent neurons. J. Chem. Neuroanat. 32(1):54-64, 2006.

Talman, W.T. Nitric Oxide and Central Cardiovascular Control: a Simple Molecule with a Complex Story. Editorial Commentary. Hypertension. 48(4):552-4, 2006.

Talman, W.T., Nitschke Dragon, D., Corr, J., Wang, D. Parasympathetic Stimulation Elicits Cerebral Vasodilatation in Rat. Autonomic Neuroscience: Basic and Clinical 2007 May 30;133(2):153-7.

Talman, W.T., Nitschke Dragon, D. Selective Neuronal Nitric Oxide Synthase Inhibition Attenuates Breakthrough of Autoregulation during Acute Hypertension. Brain Research. 1139:126-132, 2007.

Musch TI, Carroll RG, Just A, Lane PH, Talman, W.T. A broader view of animal research. BMJ. 2007 Feb 10;334 (7588):274.

Chapters
Talman, W.T., Davis PH. Myocardial damage and cardiac arrhythmias. In: Office Practice of Neurology. M. A. Samuels, S. Feske (Eds). New York: Churchill Livingstone, pp. 1199-1201, 2003.

Talman, W.T. Cardiac arrhythmias and sudden death. In: Neurological Therapeutics: Principles and Practices, John Noseworthy and M.A. Samuels (eds). Section VIII, I (b.). Martin Dunitz Publishers, pp.1255-1257, 2003.

Heistad DD, Lawton WJ, Talman, W.T. Pathogenesis of Acute Hypertensive Encephalopathy. In: Handbook of Hypertension J.L. Izzo & H.R. Black (eds). Lippincott Williams & Wilkins, Philadelphia, pp 201-203, 2003.

Talman, W.T. Parasympathetic Influences on Cerebral Circulation: a Link to Arterial Baroreflexes. In: Neural Control of Circulation N Dun (ed). Kluwer, Boston, pp 357-370, 2004.

Talman, W.T. Amino acid neurotransmission. In: Primer on the Autonomic Nervous System (2nd ed). D. Robertson, I. Biaggioni, G. Burnstock, and P.A. Low (eds). Elsevier Academic Press, Boston, pp 81-82, 2004.

Talman, WT, Lin, L.H. Glutamatergic and nitroxidergic neurotransmission in the nucleus tractus solitarii. In: Neurobiology of DOPA as a Neurotransmitter, Progress in Pharmacology and Toxicology. Misu, Y and Goshima, Y (eds) CRC Press, London, 2004.

Lab Photographs

Julie Corr, Deq Wang, Bill Talman, Li-Hsien Lin,
Deidre Nitschke Dragon, and Kristofor Agassandian after a power lunch.

Khristofor Agassandian (research scientist), Li-Hsien Lin (research scientist),
Jeffrey Riley (UI summer medical student fellow), Deoclecio Chianca
(visiting Brazilian scientist), and Deidre Nitschke Dragon.

Andrew Lawrence, visiting Australian scientist and 2002 UI Levitt Professor,
and Bill Talman collaborate in studying amino acid receptors.

Bill Talman and Li-Hsien Lin present work at the
Society for Neuroscience meeting in 2001.

Valeria Fazan (visiting Brazilian predoctoral fellow) and Khristofor
Agassandian present work at the Experimental Biology meeting in 2000.

Final preparations of a manuscript.