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Basal forebrain grafts in the hippocampus and neocortex : regulation of acetylcholine release

Nilsson, O G LU ; Leanza, G LU ; Rosenblad, C LU and Björklund, A LU (1993) In Annals of the New York Academy of Sciences 695(1). p.267-273
Abstract

The regulation of acetylcholine (ACh) release from cholinergic neurons transplanted to the hippocampus or neocortex was studied by microdialysis in awake rats. Fetal basal forebrain tissue was implanted as a cell suspension or solid graft into the fimbria-fornix-lesioned hippocampus, or as a cell suspension into the frontal cortex after excitotoxic lesion of the nucleus basalis. Several months after transplantation, microdialysis probes were implanted in areas of the hippocampus or frontal cortex reinnervated by the grafts. The grafts restored lesion-induced deficits in steady-state ACh release up to normal or above normal levels in both hippocampus and frontal cortex. The responses to KCl and tetrodotoxin suggested that the ACh release... (More)

The regulation of acetylcholine (ACh) release from cholinergic neurons transplanted to the hippocampus or neocortex was studied by microdialysis in awake rats. Fetal basal forebrain tissue was implanted as a cell suspension or solid graft into the fimbria-fornix-lesioned hippocampus, or as a cell suspension into the frontal cortex after excitotoxic lesion of the nucleus basalis. Several months after transplantation, microdialysis probes were implanted in areas of the hippocampus or frontal cortex reinnervated by the grafts. The grafts restored lesion-induced deficits in steady-state ACh release up to normal or above normal levels in both hippocampus and frontal cortex. The responses to KCl and tetrodotoxin suggested that the ACh release exhibited normal firing-dependent properties. By applying various behaviorally arousing stimuli that normally activate the basal forebrain projection systems, we wished to investigate the functional integration of the grafts in the host brain. In the hippocampus, sensory stimulation, immobilization stress and motor activity all resulted in increased release of graft-derived ACh amounting to 25-65% of the normal response. Variations in ACh levels during the day-night cycle was, however, not observed in the grafted rats. In the frontal cortex, immobilization enhanced the graft-derived ACh release (60% of normal response), whereas the response to sensory stimulation did not reach significance. Since the activity of the normal basal forebrain projection systems is under influence of monoaminergic brainstem afferents, we investigated the effects of systemic administration of amphetamine or apomorphine on ACh release in the hippocampus. Both drugs produced increases in graft-derived ACh release although the response was variable and less pronounced than normal. In conclusion, the graft-derived ACh release was affected by behavioral manipulations and catecholaminergic drugs that normally modify cholinergic septo-hippocampal and basalo-cortical activity. This strongly suggests a high degree of functional integration of the graft in the host brain allowing for a regulated release of transmitter that can be adjusted during ongoing behavior.

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keywords
Acetylcholine/metabolism, Animals, Brain Tissue Transplantation/physiology, Cerebral Cortex/metabolism, Fetal Tissue Transplantation/physiology, Hippocampus/drug effects, Motor Activity, Physical Stimulation, Potassium Chloride/pharmacology, Rats, Restraint, Physical, Stress, Psychological, Substantia Innominata/metabolism, Tetrodotoxin/pharmacology
in
Annals of the New York Academy of Sciences
volume
695
issue
1
pages
267 - 273
publisher
New York Academy of Sciences
external identifiers
  • scopus:0027374503
  • pmid:8239294
ISSN
0077-8923
DOI
10.1111/j.1749-6632.1993.tb23065.x
language
English
LU publication?
yes
id
cb8f3e79-6665-4a9c-a1c4-aa2a5b584425
date added to LUP
2019-06-25 09:57:25
date last changed
2020-01-13 02:06:23
@article{cb8f3e79-6665-4a9c-a1c4-aa2a5b584425,
  abstract     = {<p>The regulation of acetylcholine (ACh) release from cholinergic neurons transplanted to the hippocampus or neocortex was studied by microdialysis in awake rats. Fetal basal forebrain tissue was implanted as a cell suspension or solid graft into the fimbria-fornix-lesioned hippocampus, or as a cell suspension into the frontal cortex after excitotoxic lesion of the nucleus basalis. Several months after transplantation, microdialysis probes were implanted in areas of the hippocampus or frontal cortex reinnervated by the grafts. The grafts restored lesion-induced deficits in steady-state ACh release up to normal or above normal levels in both hippocampus and frontal cortex. The responses to KCl and tetrodotoxin suggested that the ACh release exhibited normal firing-dependent properties. By applying various behaviorally arousing stimuli that normally activate the basal forebrain projection systems, we wished to investigate the functional integration of the grafts in the host brain. In the hippocampus, sensory stimulation, immobilization stress and motor activity all resulted in increased release of graft-derived ACh amounting to 25-65% of the normal response. Variations in ACh levels during the day-night cycle was, however, not observed in the grafted rats. In the frontal cortex, immobilization enhanced the graft-derived ACh release (60% of normal response), whereas the response to sensory stimulation did not reach significance. Since the activity of the normal basal forebrain projection systems is under influence of monoaminergic brainstem afferents, we investigated the effects of systemic administration of amphetamine or apomorphine on ACh release in the hippocampus. Both drugs produced increases in graft-derived ACh release although the response was variable and less pronounced than normal. In conclusion, the graft-derived ACh release was affected by behavioral manipulations and catecholaminergic drugs that normally modify cholinergic septo-hippocampal and basalo-cortical activity. This strongly suggests a high degree of functional integration of the graft in the host brain allowing for a regulated release of transmitter that can be adjusted during ongoing behavior.</p>},
  author       = {Nilsson, O G and Leanza, G and Rosenblad, C and Björklund, A},
  issn         = {0077-8923},
  language     = {eng},
  number       = {1},
  pages        = {267--273},
  publisher    = {New York Academy of Sciences},
  series       = {Annals of the New York Academy of Sciences},
  title        = {Basal forebrain grafts in the hippocampus and neocortex : regulation of acetylcholine release},
  url          = {http://dx.doi.org/10.1111/j.1749-6632.1993.tb23065.x},
  doi          = {10.1111/j.1749-6632.1993.tb23065.x},
  volume       = {695},
  year         = {1993},
}