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Characterization of in vivo noradrenaline release from superior cervical ganglia or fetal locus coeruleus transplanted to the subcortically deafferented hippocampus in the rat

Cenci, M A LU ; Nilsson, O G LU ; Kalén, P LU and Björklund, A LU (1993) In Experimental Neurology 122(1). p.73-87
Abstract

Solid grafts of autologous superior cervical ganglia (SCG) or fetal locus coeruleus (LC) were implanted unilaterally into a fimbria-fornix lesion cavity adjacent to the hippocampal formation after a 6-hydroxydopamine lesion of the intrinsic noradrenergic system. Twelve to 15 months after transplantation, one microdialysis probe was implanted in the dorsal hippocampus ipsilateral to the graft, and extracellular levels of noradrenaline (NA) were monitored during the application of pharmacological or behavioral stimuli. Age-matched intact and lesion-only animals served as controls. Morphological examination of the grafts was performed on sections processed for dopamine-beta-hydroxylase (DBH) immunohistochemistry. In the lesion-only... (More)

Solid grafts of autologous superior cervical ganglia (SCG) or fetal locus coeruleus (LC) were implanted unilaterally into a fimbria-fornix lesion cavity adjacent to the hippocampal formation after a 6-hydroxydopamine lesion of the intrinsic noradrenergic system. Twelve to 15 months after transplantation, one microdialysis probe was implanted in the dorsal hippocampus ipsilateral to the graft, and extracellular levels of noradrenaline (NA) were monitored during the application of pharmacological or behavioral stimuli. Age-matched intact and lesion-only animals served as controls. Morphological examination of the grafts was performed on sections processed for dopamine-beta-hydroxylase (DBH) immunohistochemistry. In the lesion-only controls, the hippocampus was totally devoid of DBH-immunoreactive fibers and hippocampal levels of NA were generally undetectable. Although both SCG and LC grafts gave rise to an extensive DBH-immunoreactive fiber ingrowth in the ipsilateral hippocampus, baseline NA release was strikingly different in the two graft groups, being markedly lower than normal in the SCG-grafted rats (3.5 +/- 0.1 fmol/30 microliters) and significantly higher than normal in the LC-grafted rats (44.5 +/- 12.3 fmol/30 microliters). The response to potassium-induced depolarization (100 mM KCl in the perfusion fluid), neuronal uptake blockade (5 microM desipramine), and sodium-channel blockade (1 microM TTX) was similar to normal in both graft groups. Exposure of the animals to mild (handling) or severe (immobilization) stressful stimuli significantly enhanced NA release in the intact controls, whereas no clear-cut effect could be detected in either graft group. Electrical stimulation of the medial septum, applied in an attempt to activate possible afferents to the grafts from the host septum, did not enhance NA release in any of the groups. The results show that grafts of both central and peripheral noradrenergic neurons can provide a source of steady-state NA release in the denervated hippocampus, but that the spontaneous activity of the grafted ganglionic neurons is very low compared to that of the LC neurons, probably due to the absence of a functional preganglionic input to the grafted SCG neurons. Although extracellular NA recovered from both the SCG- and the LC-grafted hippocampi is likely to derive from impulse-dependent neuronal release, it was largely unaffected by physiological stimuli applied to the host.

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published
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keywords
Afferent Pathways/physiology, Animals, Brain Tissue Transplantation, Denervation, Dialysis, Female, Fetal Tissue Transplantation, Ganglia, Sympathetic/metabolism, Handling (Psychology), Hippocampus/metabolism, Immobilization, Locus Coeruleus/metabolism, Nerve Tissue/transplantation, Norepinephrine/metabolism, Rats, Rats, Sprague-Dawley
in
Experimental Neurology
volume
122
issue
1
pages
73 - 87
publisher
Academic Press
external identifiers
  • scopus:0027185937
  • pmid:8339791
ISSN
0014-4886
DOI
10.1006/exnr.1993.1109
language
English
LU publication?
yes
id
377e48f9-64a5-4219-9ae0-5612b36336b0
date added to LUP
2019-06-25 10:01:16
date last changed
2020-01-13 02:06:35
@article{377e48f9-64a5-4219-9ae0-5612b36336b0,
  abstract     = {<p>Solid grafts of autologous superior cervical ganglia (SCG) or fetal locus coeruleus (LC) were implanted unilaterally into a fimbria-fornix lesion cavity adjacent to the hippocampal formation after a 6-hydroxydopamine lesion of the intrinsic noradrenergic system. Twelve to 15 months after transplantation, one microdialysis probe was implanted in the dorsal hippocampus ipsilateral to the graft, and extracellular levels of noradrenaline (NA) were monitored during the application of pharmacological or behavioral stimuli. Age-matched intact and lesion-only animals served as controls. Morphological examination of the grafts was performed on sections processed for dopamine-beta-hydroxylase (DBH) immunohistochemistry. In the lesion-only controls, the hippocampus was totally devoid of DBH-immunoreactive fibers and hippocampal levels of NA were generally undetectable. Although both SCG and LC grafts gave rise to an extensive DBH-immunoreactive fiber ingrowth in the ipsilateral hippocampus, baseline NA release was strikingly different in the two graft groups, being markedly lower than normal in the SCG-grafted rats (3.5 +/- 0.1 fmol/30 microliters) and significantly higher than normal in the LC-grafted rats (44.5 +/- 12.3 fmol/30 microliters). The response to potassium-induced depolarization (100 mM KCl in the perfusion fluid), neuronal uptake blockade (5 microM desipramine), and sodium-channel blockade (1 microM TTX) was similar to normal in both graft groups. Exposure of the animals to mild (handling) or severe (immobilization) stressful stimuli significantly enhanced NA release in the intact controls, whereas no clear-cut effect could be detected in either graft group. Electrical stimulation of the medial septum, applied in an attempt to activate possible afferents to the grafts from the host septum, did not enhance NA release in any of the groups. The results show that grafts of both central and peripheral noradrenergic neurons can provide a source of steady-state NA release in the denervated hippocampus, but that the spontaneous activity of the grafted ganglionic neurons is very low compared to that of the LC neurons, probably due to the absence of a functional preganglionic input to the grafted SCG neurons. Although extracellular NA recovered from both the SCG- and the LC-grafted hippocampi is likely to derive from impulse-dependent neuronal release, it was largely unaffected by physiological stimuli applied to the host.</p>},
  author       = {Cenci, M A and Nilsson, O G and Kalén, P and Björklund, A},
  issn         = {0014-4886},
  language     = {eng},
  number       = {1},
  pages        = {73--87},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Characterization of in vivo noradrenaline release from superior cervical ganglia or fetal locus coeruleus transplanted to the subcortically deafferented hippocampus in the rat},
  url          = {http://dx.doi.org/10.1006/exnr.1993.1109},
  doi          = {10.1006/exnr.1993.1109},
  volume       = {122},
  year         = {1993},
}