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

Students

Greta Gnanamanickam, PhD Student

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 University Profile Page

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.

Selected Recent Publications

Llewellyn-Smith IJ (2009) Anatomy of synaptic circuits controlling the activity of sympathetic preganglionic neurons. Journal of Chemical Neuroanatomy, 38(3), 231-239

Pajolla GP, Accorsi-Mendonça D, Lunardi CN, Bendhack LM, Machado BH & Llewellyn-Smith IJ (2009) Immunoreactivity for neuronal NOS and fluorescent indication of NO formation in the NTS of juvenile rats submitted to chronic intermittent hypoxia. Autonomic Neuroscience-Basic and Clinical, 148(1-2), 55-62

Hinrichs JM & Llewellyn-Smith IJ (2009) Variability in the occurrence of nitric oxide synthase immunoreactivity in different populations of rat sympathetic preganglionic neurons. Journal of Comparative Neurology, 514(5), 492-506

Neumann S, Braz JM, Skinner K, Llewellyn-Smith IJ & Basbaum AI (2008) Innocuous, not noxious, input activates PKCgamma interneurons of the spinal dorsal horn via myelinated afferent fibers. Journal of Neuroscience, 28(32), 7936-7944

Peters JH, McDougall SJ, Kellett DO, Jordan D, Llewellyn-Smith IJ & Andresen MC (2008) Oxytocin enhances cranial visceral afferent synaptic transmission to the solitary tract nucleus. Journal of Neuroscience, 28(45), 11731-11740

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

 

Updated March 14, 2012