Somatic nerve stimulation evokes qualitatively different somatosympathetic responses in the cervical and splanchnic sympathetic nerves in the rat

Full cite: S. McMullan, et al. Somatic nerve stimulation evokes qualitatively different somatosympathetic responses in the cervical and splanchnic sympathetic nerves in the rat. Brain Res., 1217 (2008), pp. 139–147 Simon McMullan, Karrnan Pathmanandavel, Paul M. Pilowsky, Ann K. Goodchild Australian School of Advanced Medicine, Macquarie University, Australia University of Sydney This study is examining the reflex responses of two different sympathetic nerves in response to somatic pressor response– from the sciatic nerve. The two sympathetic nerves that they are looking at is the splanchnic and cervical nerve. The primary technique used is this study is electrophysiology. They stimulated from the aortic depressor nerve, using antidromic action potentials to confirm that the neurons that they were recording from in RVLM were barosensitive. They found that the splanchnic nerve had a primarily biphasic response to sciatic nerve stimulation, whereas the cervical nerve was primarily monophasic. This suggests qualitatively different responses between the sympathetic nerves given the same stimulus, suggesting a difference in the pathways controlling these nerves. It was determined that the first peak in both cervical and splanchnic were mediated throughout the same pathway, however, the second peak of the splanchnic –which was not present in the cervical– was due to an additional response in the splanchnic to the stimulus. This additional response to the splanchnic might be likely due to some input from unmyelinated afferents, that are selectively absent in the cervical control. The splanchnic receives both A- and C- fibers, whereas the cervical only receives A- fibers, suggesting a non-uniform organizational scheme when it comes to the control of RVLM. This paper provides a little bit of additional evidence into the complexity of RVLM’s control of the sympathetic nervous system, and that each sympathetic nerve has different properties to its control and function. There are likely different neurons controlling the different nerve activities, but also different afferents projecting to these nerves. My presentation and the study paired with it is another piece of evidence to RVLM’s sympathetic control, showing that adrenal and splanchnic control are mediated differentially by GABA following baroreflex unloading. -MTL

Lateralisation of projections from the rostral ventrolateral medulla to sympathetic preganglionic neurons in the rat

Lateralisation of projections from the rostral ventrolateral medulla to sympathetic preganglionic neurons in the rat Elizabeth A. Moon, Ann K. Goodchild, Paul M. Pilowsky Hypertension and Stroke Research Laboratories, Departments of Physiology and Neurosurgery, University of Sydney, Block 3 Ground Floor, Royal North Shore Hospital, St. Leonards, 2065 Sydney, NSW, Australia This study contains three different techniques: anterograde tract-tracing (using Phaseolus vulgaris leucoagglutinin, PHA-L), retrograde tract-tracing(using CTB) and electrophysiology. Spinally projecting neurons (SPNs) that project to the adrenal gland or to the superior cervical ganglia were labelled retrogradely. The retrograde labeling was paired with anterograde tract-tracing from the RVLM to see if lateralization in the bulbospinal projection to SPN innervating the adrenal gland or superior cervical ganglia could be identified. Unilateral injections of the spinal cord were made with a retrograde tracer in order to determine the amount of lateralization between the upper and lower thoracic spinal cord. The last experiment they did was stimulate the RVLM with glutamate and record from the left cervical sympathetic and left adrenal nerve to test for functional lateralization. They found that the SPNs controlling the SCG were primarily bilateral, meaning that both the ipsilateral and contralateral sides were nearly equally labelled following anterograde labeling. The SPNs controlling the adrenal medulla were almost exclusively labelled on the ipsilateral side, suggesting ipsilateral control. Next in the retrograde tracing studies, they showed that CTB injected unilaterally at T2 and T8 both showed about 66%-75% ipsilateral projections to 25%-33% contralateral projections. The electrophysiological studies showed that following glutamatergic stimulation of RVLM, there are no differences in the ratio of responses to either the cervical sympathetic truck or adrenal nerve, suggesting that while there are differences in anatomical connections, the functional contribution of each RVLM to the respective nerve activity may very well be the same under the given conditions. This paper will provide helpful anatomical knowledge for my presentation where I will present my differential control data. My results corroborate with their anatomy data for the adrenal nerve, demonstrating that under normotensive conditions, that the adrenal nerve responds the primarily ipsilateral to a given injection of glutamate. It would be interesting to do a similar tract tracing study to see if the nature of the ipsilateral/contralateral connections might be altered following physical (in)-activity. -MTL

The ventrolateral medulla and sympathetic regulation of arterial pressure.

ANN M. SCHREIHOFER AND ALAN F. SVED.  The ventrolateral medulla and sympathetic regulation of arterial pressure. In: Central regulation of autonomic functions.  2^nd Edition. Eds: I.J. Llewellyn-Smith and A.J. Verberne Oxford University Press, Inc. New York, 2011.

So in honor of our guest from Australia I thought it was timely to provide a posting on one of the chapters from Ida's recent book that will likely be considered the bible on neural control for at least the next 5-10 years.  The particular chapter I chose is of course most relevant to our studies on the RVLM, although other chapters in this book are also important in terms of our understanding of brainstem control of arterial pressure.  In this chapter Ann Schreihofer and Alan Sved provide a nice overview of the history and development of what the current knowledge is on brainstem control of sympathetic outflow.  They do a great job in discussing the number of techniques used to examine the ventrolateral medulla in term of it's anatomy and physiology.  Several nice figures combine immunohistochemistry, histology, BP and SNA responses etc. to illustrate the relationship between the CVLM and the RVLM.  There is also some clarification on the confusion caused by the original nomenclature of the C1 cells and that while serving as a useful marker for barosensitive, bulbospinal neurons controlling SNA, use glutamate not epinephrine serves as the primary neurotransmitters of RVLM neurons.  A thorough discussion of the roles of the RVLM and CVLM is provided.   There is a section of the caudal pressor area which while interesting, seems to pale in comparison to the importance of the CVLM and RVLM.  Finally, the last two sections are devoted to differential control and the role of the VLM in hypertension.  Both nice summaries but also highlight the number of unaswered questions that remain to be answered, some of which are being addressed in our laboratory.  Overall this is a chapter that every student, postdoc and faculty working in the field needs to be well-versed in so if you haven't done so recently or already, I would suggest giving it a look soon.

Posted by Pat

Hot off the press! Patterning of somatosympathetic reflexes reveals non-uniform organization of presympathetic drive from C1 and non-C1 RVLM neurons

It is well known that activation of muscle afferents by contracting muscle causes an increase in blood pressure. This is known as the somatopressor reflex. The reflex is driven by the SNS, and neurons in the RVLM mediate it. Some differential patterning of responses between different sympathetic nerves has been observed before, but not thoroughly investigated. This study investigates differential sympathetic nerve responses to graded activation of the afferent arm of the sciatic nerve, a.k.a. the somatosympathetic reflex. Furthermore, the relative contributions of C1 to non-C1 neurons in this response were examined.
Briefly, anesthetized rats were instrumeted to record arterial pressure and sympathetic activity from four nerves, cervical, splanchnic, lumbar, and renal. Stimulating electrodes were implanted on the left or right sciatic nerve. They performed sciatic nerve stimulation (ScNS) at varying intensities and amplitudes in normal rats. An additional set of experiments was performed in C1 neuron-depleted rats in which only splanchnic SNA was recorded.
Under normal conditions, ScNS produced double-peak responses in all but the cervical nerve. The peaks in the lumbar and renal nerves had slightly longer latency than splanchnic and cervical. In addition, the first peak of the splanchnic nerve was of larger amplitude than the second, but the opposite was seen in renal and lumbar nerves. In rats which had about 60% depletion of C1 neurons, the second peak in splanchnic SNA was abolished, but the first peak was only slightly attenuated.
These results suggest that, indeed, different sympathetic nerves have specific roles in the SNS response to muscle contraction. Moreover, C1 and non-C1 neurons are both involved in the response, each producing distinct peaks in splanchnic SNA, possibly according to the conduction velocity of their axons (C1 fast, non-C1 slow). This study provides even more evidence that SNA to specific vascular beds may be differentially controlled. It also highlights the importance of recording from multiple versus a single sympathetic output(s) in a single animal when performing in vivo experiments.
-Nick