Effects of spinal cord injury on synaptic inputs to sympathetic preganglionic neurons

https://doi.org/10.1016/S0079-6123(05)52001-6Get rights and content

Abstract

Spinal cord injuries often lead to disorders in the control of autonomic function, including problems with blood pressure regulation, voiding, defecation and reproduction. The root cause of all these problems is the destruction of brain pathways that control spinal autonomic neurons lying caudal to the lesion. Changes induced by spinal cord injuries have been most extensively studied in sympathetic preganglionic neurons, cholinergic autonomic neurons with cell bodies in the lateral horn of thoracic and upper lumbar spinal cord that are the sources of sympathetic outflow. After an injury, sympathetic preganglionic neurons in mid-thoracic cord show plastic changes in their morphology. There is also extensive loss of synaptic input from the brain, leaving these neurons profoundly denervated in the acute phase of injury. Our recent studies on sympathetic preganglionic neurons in lower thoracic and upper lumbar cord that regulate the pelvic viscera suggest that these neurons are not so severely affected by spinal cord injury. Spinal interneurons appear to contribute most of the synaptic input to these neurons so that injury does not result in extensive denervation. Since intraspinal circuitry remains intact after injury, drug treatments targeting these neurons should help to normalize sympathetically mediated pelvic visceral reflexes. Furthermore, sympathetic pelvic visceral control may be more easily restored after an injury because it is less dependent on the re-establishment of direct synaptic input from regrowing brain axons.

Section snippets

Location and morphology of sympathetic preganglionic neurons

Sympathetic preganglionic neurons are small- to medium-sized cholinergic neurons and their cell bodies are located in the thoracic and upper lumbar spinal cord in four distinct subnuclei within the lateral horn (Cabot, 1990). The majority of sympathetic preganglionic somata occur in the intermediolateral cell column, which lies at the border between the grey and white matter of the spinal cord. In the intermediolateral cell column, the cell bodies of sympathetic preganglionic neurons are

Innervation of sympathetic preganglionic neurons in intact and injured cord

In intact cord, sympathetic preganglionic neurons are innervated by both supraspinal and intraspinal neurons. Virus tracing studies have been particularly useful for revealing the locations of presympathetic neurons, i.e., those that are directly antecedent to sympathetic preganglionic neurons and are likely to be involved in regulating their activity. Supraspinal inputs to sympathetic preganglionic neurons come from five main brain regions, including the rostral ventrolateral medulla, the

Rostrocaudal differences in sympathetic preganglionic neurons and their innervation

The sympathetic nervous system was originally thought to act in an undifferentiated way to allow an animal to respond appropriately to life-threatening situations. However, over the past two decades, it has become increasingly clear that central control of sympathetic outflow is differential, permitting specific functional groups of sympathetic preganglionic neurons to respond in different ways to the same homeostatic challenge (reviewed by Morrison, 2001). Differences in the spatial

Acknowledgments

Project Grants (#229907 to ILS and #000044 to JRK) and Research Fellowships (#229921 to ILS and #358709 to JRK) from the National Health and Medical Research Council of Australia, grants from the National Heart Foundation of Australia (#G98A0097 and #G00A0512 to ILS), a Visiting Scientist Award from the Heart and Stroke Foundation of Canada (ILS), Ontario Heart and Stroke Foundation (LCW) and the Canadian Institutes of Health Research (LCW) supported this work. Carolyn Martin, Natalie Fenwick

References (84)

  • S.A. Deuchars et al.

    Properties of interneurones in the intermediolateral cell column of the rat spinal cord: role of the potassium channel subunit Kv3.1

    Neuroscience

    (2001)
  • V. Holets et al.

    The differential distribution and relationship of serotonergic and peptidergic fibers to sympathoadrenal neurons in the intermediolateral cell column of the rat: a combined retrograde axonal transport and immunofluorescence study

    Neuroscience

    (1982)
  • H. Inokuchi et al.

    Fast excitatory postsynaptic potentials and the responses to excitant amino acids of sympathetic preganglionic neurons in the slice of the cat spinal cord

    Neuroscience

    (1992)
  • A.S.P. Jansen et al.

    Transneuronal labeling of CNS neuropeptide and monoamine neurons after pseudorabies virus injections into the stellate ganglion

    Brain Res.

    (1995)
  • S. Joshi et al.

    Identification of spinal interneurons antecedent to adrenal sympathetic preganglionic neurons using trans-synaptic transport of herpes simplex virus type 1

    Neuroscience

    (1995)
  • K. Kadzielawa

    Inhibition of the activity of sympathetic preganglionic neurones and neurones activated by visceral afferents, by alpha-methylnoradrenaline and endogenous catecholamines

    Neuropharmacology

    (1983)
  • A.V. Krassioukov et al.

    Morphological changes in sympathetic preganglionic neurons after spinal cord injury in rats

    Neuroscience

    (1996)
  • N.R. Krenz et al.

    Changes in the morphology of sympathetic preganglionic neurons parallel the development of autonomic dysreflexia after spinal cord injury in rats

    Neurosci. Lett.

    (1998)
  • N.R. Krenz et al.

    Sprouting of primary afferent fibers after spinal cord transection in the rat

    Neuroscience

    (1998)
  • C.C. Lai et al.

    Excitatory action of pituitary adenylate cyclase activating polypeptide on rat sympathetic preganglionic neurons in vivo and in vitro

    Brain Res.

    (1997)
  • D.I. Lewis et al.

    Excitation and inhibition of rat sympathetic preganglionic neurons by catecholamines

    Brain Res.

    (1990)
  • I.J. Llewellyn-Smith et al.

    GABA- and glutamate-immunoreactive synapses on sympathetic preganglionic neurons projecting to the superior cervical ganglion

    J. Auton. Nerv. Syst.

    (1998)
  • I.J. Llewellyn-Smith et al.

    Glutamate- and GABA-immunoreactive synapses on sympathetic preganglionic neurons caudal to a spinal cord transection in rats

    Neuroscience

    (1997)
  • I.J. Llewellyn-Smith et al.

    Glutamate immunoreactive synapses on retrogradely labelled sympathetic neurons in rat thoracic spinal cord

    Brain Res.

    (1992)
  • A.D. Loewy et al.

    Serotonergic projections from the ventral medulla to the intermediolateral cell column in the rat

    Brain Res.

    (1981)
  • R.C. Ma et al.

    Norepinephrine depolarizes lateral horn cells of neonatal rat spinal cord in vitro

    Neurosci. Lett.

    (1985)
  • R.C. Ma et al.

    Vasopressin depolarizes lateral horn cells of the neonatal rat spinal cord in vitro

    Brain Res.

    (1985)
  • R.C. Ma et al.

    Excitation of lateral horn neurons of the neonatal rat spinal cord by 5-hydroxytryptamine

    Dev. Brain Res.

    (1986)
  • T.A. Milner et al.

    Phenylethanolamine N-methyltransferase-containing terminals synapse directly on sympathetic preganglionic neurons in the rat

    Brain Res.

    (1988)
  • J.B. Minson et al.

    Neuropeptide Y mRNA expression in interneurons in rat spinal cord

    Auton. Neurosci.

    (2001)
  • J.B. Minson et al.

    Bulbospinal neuropeptide Y-immunoreactive neurons in the rat: comparison with adrenaline-synthesising neurons

    J. Auton. Nerv. Syst.

    (1994)
  • J. Minson et al.

    Glutamate in spinally projecting neurons of the rostral ventral medulla

    Brain Res.

    (1991)
  • T. Miyazaki et al.

    Excitatory and inhibitory effects of epinephrine on neonatal rat sympathetic preganglionic neurons in vitro

    Brain Res.

    (1989)
  • N. Mo et al.

    Excitatory postsynaptic potentials in neonatal rat sympathetic preganglionic neurons: possible mediation by NMDA receptors

    Neurosci. Lett.

    (1987)
  • N. Mo et al.

    Is glycine an inhibitory transmitter in rat lateral horn cells?

    Brain Res.

    (1987)
  • B.W. Newton et al.

    Immunohistochemical demonstration of serotonin neurons in autonomic regions of the rat spinal cord

    Brain Res.

    (1986)
  • A.B. Ondarza et al.

    Direct evidence of primary afferent sprouting in distant segments following spinal cord injury in the rat: colocalization of GAP-43 and CGRP

    Exp. Neurol.

    (2003)
  • C.A. Sasek et al.

    Evidence for co-existence of thyrotropin-releasing hormone, substance P and serotonin in ventral medullary neurons that project to the intermediolateral cell column in the rat

    Neuroscience

    (1990)
  • A.M. Strack et al.

    A general pattern of CNS innervation of the sympathetic outflow demonstrated by transneuronal pseudorabies viral infections

    Brain Res.

    (1989)
  • A.M. Strack et al.

    Spinal origin of sympathetic preganglionic neurons in the rat

    Brain Res.

    (1988)
  • X. Tang et al.

    Spinal interneurons infected by renal injection of pseudorabies virus in the rat

    Brain Res.

    (2004)
  • L.C. Weaver et al.

    Changes in immunoreactivity for growth associated protein-43 suggest reorganization of synapses on spinal sympathetic neurons after cord transection

    Neuroscience

    (1997)
  • Cited by (0)

    View full text