Cardiovascular Neuroscience Laboratory

Double immunoperoxidase labelling for nitric oxide synthase (NOS) and choline acetyl transferase (ChAT) in the lateral horn of rat upper thoracic spinal cord. Transverse section stained first for NOS with a black reaction product and then for ChAT with a brown reaction product. A, Low magnification micrograph of segment T2. Arrows B and C indicate areas shown at higher power in B and C. B and C, Brown ChAT-immunoreactive neurons (arrows) are intermixed with black NOS-immunoreactive neurons (arrowheads) both in the central autonomic area (CAA), which lies above the central canal (cc), and in the intermediolateral cell column (IML), where the cell bodies of most sympathetic preganglionic neurons are located. Bars: A = 250 µm, B and C = 50 µm.

Nerves in the brain and spinal cord regulate blood pressure by the integrated control of blood vessel diameter, heart function and hormone release. This nerve activity ensures that blood pressure is maintained at a level adequate to supply important organs, such as the brain and the heart, and that oxygen supply matches changing tissue requirements. The primary aim of our laboratory is to identify the nerves in the brain and spinal cord that control blood pressure and to characterize their connections. We use labels that are visible with light and electron microscopes to determine whether nerves in one region “talk to” nerves in another region, to identify what neurotransmitter chemicals these nerves use to communicate and to establish what receptors the nerves use to bind the neurotransmitters. In physiological studies, we inject transmitter-related drugs into the brain to see how the drugs affect blood pressure. In our experiments we use not only normal animals but also animals in which blood pressure control has been disrupted by spinal cord injury. The information that we gain from our studies is important for understanding how the central nervous system controls blood pressure in both health and disease.

Investigators

Ida Llewellyn-Smith, AB(Hons), PhD

Visiting Research Fellows / Scholars

Julia Hinrichs, Honours student, Universidade Federal de São Paulo, São Paulo, Brazil

Support Staff

Lee Travis

Contacts

Assoc Prof Ida Llewellyn-Smith

Ph: (08) 8204 4456 Int Ph: +61 8 8204 4456 Fax: (08) 8204 5268 Int Fax: +61 8 8204 5268 Email: ida.llewellyn-smith@flinders.edu.au

Research Projects

• Chronic heart failure induces changes in autonomic nerve pathways in the paraventricular nucleus of the hypothalamus
• Nitric oxide synthase immunoreactivity in sympathetic preganglionic neurons
• Innervation of sacral autonomic neurons by axons containing corticotropin releasing factor
• Activation of micturition-related sacral spinal neurons differs between rats with normal and overactive bladder

Collaborative Research

Our collaboration with Dr Ann Schreihofer (Medical College of Georgia, Augusta GA USA) continues. A joint study on the innervation of spinal autonomic areas by neurons that express vesicular glutamate transporters 1 and 2 was completed and published. A new study to identify enkephalin-synthesizing neurons in the hypothalamus was initiated.

Despite the death of Prof David Jordan (Royal Free Hospital School of Medicine, London), experiments on defining the neurotransmitters that control barosensitive neurons in the nucleus of the solitary tract continue using neurons in the nucleus of the solitary tact (NTS) that were juxtacellularly labelled in the Jordan laboratory and sent to Flinders for immunohistochemical processing. A study on oxytocin innervation of juxtacellularly labelled NTS is nearing completion.

Dr Janet Keast , Prince of Wales Medical Research Institute, Sydney, continues to collaborate with the laboratory in investigating how neuronal circuits controlling the bladder, bowel and reproductive organs after a spinal cord injury. A new joint project examining how sympathetic post-ganglionic neurons innervating uterine smooth muscle and blood vessels change in pregnancy also began.

Work with Dr Tony Verberne and Daniela Sartor, his post-doctoral associate, (Department of Medicine, Austin & Repatriation Medical Centre, Melbourne) on juxtacellularly labelled RVLM neurons continues. A study examining the serotonergic input to juxtacellularly labelled bulbospinal barosensitive RVLM neuron is nearing completion. Preliminary data was also generated for an NHMRC grant on RVLM neurons controlling adrenaline release from the adrenal medulla in normal and diabetic rats.

Media Appearances

HealthOrbit (an online health related news service that covers all the news and developments in the health industry), Spinal nerves, not the brain, calls the shots in the pelvic organs, March 2005

Radio Australia, Australian breakthrough in spinal cord research, 2 February 2005

ABC News Online, Spinal cord key to sexual dysfunction, 2 February 2005

The West Australian, Spinal pointer linked to sex problems, 2 February 2005

Patents

IJ Llewellyn-Smith: US Patent #6,376,460 B2 - Issued 23 April 2002, A Method of Modulating Cellular Activity

Publications

Llewellyn-Smith IJ, Martin CL, Fenwick NM, Dicarlo SE, Lujan HL, Schreihofer AM. (2007) VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord. J Comp Neurol. 503(6):741-67

Llewellyn-Smith IJ, Weaver LC, Keast JR. (2006) Effects of spinal cord injury on synaptic inputs to sympathetic preganglionic neurons. Prog Brain Res. 152:11-26. Review

Fenwick NM , Martin CL, Llewellyn-Smith IJ. (2006) Immunoreactivity for cocaine- and amphetamine-regulated transcript in rat sympathetic preganglionic neurons projecting to sympathetic ganglia and the adrenal medulla. J Comp Neurol. 495(4):422-33

Llewellyn-Smith IJ, Weaver LC and Keast JR: (2005) Effects of spinal cord injury on synaptic inputs to sympathetic preganglionic neurons. Prog Brain Res 152: 11-26

Llewellyn-Smith IJ, Dicarlo SE, Collins HL, Keast JR: (2005) Enkephalin-immunoreactive interneurons extensively innervate sympathetic preganglionic neurons regulating the pelvic viscera. Journal of Comparative Neurology 488(3):278-89

Burman KJ, Sartor DM, Verberne AJ, Llewellyn-Smith IJ: (2004) Cocaine- and amphetamine-regulated transcript in catecholamine and noncatecholamine presympathetic vasomotor neurons of rat rostral ventrolateral medulla. Journal of Comparative Neurology 476(1):19-31

Burman KJ, Ige A, White J, Marshall F, Emson PC, Minson JB and Llewellyn-Smith IJ: (2003) GABAB receptor subunits, R1 and R2, in brainstem catecholamine and serotonin neurons. Brain Research 970(1-2):35-46

Llewellyn-Smith IJ, Martin CL, Marcus JN, Yanagisawa M, Minson JB, Scammell TE: (2003) Orexin-immunoreactive inputs to rats sympathetic pregangionic neurons. Neurosci Lett 351(2):115-9

Somogyi J. (2002) Differences in ratios of GABA, glycine and glutamate immunoreactivities in nerve terminals on rat hind limb motoneurons: A possible source of post-synaptic variability. Brain Res Bull 59: 151-161

Llewellyn-Smith IJ (2002) GABA in the control of sympathetic preganglionic neurons. Clin Exp Pharmacol Physiol 29 :507-13

Llewellyn-Smith IJ, Martin CL and Minson JB. (2002) Glutamate and GABA content of calbindin-immunoreactive nerve terminals in the rat intermediolateral cell column. Auton Neurosci 98: 7-11

Minson JB, Arnolda LF and Llewellyn-Smith IJ. (2002) Neurochemistry of nerve fibres apposing sympathetic preganglionic neurons activated by sustained hypotension. J Comp Neurol 449: 307-318

Guyenet PG, Stornetta RL, Schreihofer AM, Pelaez NM, Hayar A, Aicher S and Llewellyn-Smith IJ. (2002) Opioid signalling in the rat rostral ventrolateral medulla. Clin Exp Pharmacol Physiol 29: 238-242

Jones GA, Llewellyn-Smith IJ and Jordan D. (2002) Physiological, pharmacological and immunohistochemical characterisation of juxtacellularly labelled neurones in rat nucleus tractus solitarius. Auton Neurosci 98: 12-16

Llewellyn-Smith IJ, Weaver LC (2001) Changes in synaptic inputs to sympathetic preganglionic neurons after spinal cord injury. J Comp Neurol. 25; 435(2):226-40

Llewellyn-Smith IJ, Schreihofer AM and Guyenet PG: (2001) Distribution and amino acid content of enkephalin-immunoreactive inputs on juxtacellularly labeled bulbospinal barosensitive neurons. Neuroscience 108: 307-322

Burman KJ , McKitrick DJ, Minson JB, West A, Arnolda LF and Llewellyn-Smith IJ: (2001) Neurokinin-1 receptor immunoreactivity in hypotension sensitive sympathetic preganglionic neurons. Brain Res. 915: 238-243

Minson JB, Llewellyn-Smith IJ and Arnolda LF: (2001) Neuropeptide Y-expressing interneurons in rat spinal cord. Autonomic Neuroscience 93: 14-20

Somogyi J and Llewellyn-Smith IJ: (2001) Patterns of co-localization of GABA, glutamate and glycine immunoreactivities in terminals that synapse on noradrenergic neurons in rat locus coeruleus. Eur J Neurosci 14: 219-228

Goodchild AK, Llewellyn-Smith IJ, Sun QJ, Chalmers J, Cunningham AM, Pilowsky PM: (2000) Calbindin-immunoreactive neurons in the reticular formation of the rat brainstem: catecholamine content and spinal projections. Journal of Comparative Neurology 424(3):547-62

McKitrick DJ: (2000) Expression of fos in the hypothalamus of rats exposed to warm and cold temperatures. Brain Research Bulletin 53(3):307-15

Burman K, Darian-Smith C, Darian-Smith I: (2000) Geometry of rubrospinal, rubroolivary, and local circuit neurons in the macaque red nucleus. Journal of Comparative Neurology 423(2):197-219

Burman K, Darian-Smith C, Darian-Smith I: (2000) Macaque red nucleus: origins of spinal and olivary projections and terminations of cortical inputs. Journal of Comparative Neurology 423(2):179-96

Arnolda LF, McKitrick DJ, Llewellyn-Smith IJ, Minson JB: (2000) Nitric oxide limits pressor responses to sympathetic activation in rat spinal cord. Hypertension 36(6): 1089-92

Llewellyn-Smith IJ, Martin CL, Arnolda LF, Minson JB: (2000) Tracer-toxins: cholera toxin B-saporin as a model. Journal of Neuroscience Methods 103(1):83-90

Updated December 15, 2009