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Grafted septal neurons form cholinergic synaptic connections in the dentate gyrus of behaviorally impaired aged rats

Clarke, D J ; Gage, F H ; Nilsson, O G LU and Björklund, A LU orcid (1986) In Journal of Comparative Neurology 252(4). p.92-483
Abstract

A group of aged, behaviorally impaired rats received suspension grafts of fetal septal-diagonal band tissue into the otherwise intact hippocampal formation. Three months after grafting, behaviorally recovered rats were studied by immunocytochemistry by using monoclonal antibodies to choline acetyltransferase (ChAT) and electron microscopy. The innervation of the host dentate gyrus by graft-derived ChAT-positive fibres was unmasked by acute removal of the intrinsic septal cholinergic innervation by fimbria-fornix transection 5-7 days before perfusion. The pattern of termination and ultrastructural connectivity were compared with previous results obtained from both young nonoperated control animals and a group of young rats with... (More)

A group of aged, behaviorally impaired rats received suspension grafts of fetal septal-diagonal band tissue into the otherwise intact hippocampal formation. Three months after grafting, behaviorally recovered rats were studied by immunocytochemistry by using monoclonal antibodies to choline acetyltransferase (ChAT) and electron microscopy. The innervation of the host dentate gyrus by graft-derived ChAT-positive fibres was unmasked by acute removal of the intrinsic septal cholinergic innervation by fimbria-fornix transection 5-7 days before perfusion. The pattern of termination and ultrastructural connectivity were compared with previous results obtained from both young nonoperated control animals and a group of young rats with intrahippocampal septal grafts that had been subjected to denervation of the intrinsic cholinergic input at the time of transplantation. Graft-derived, ChAT-immunoreactive terminals formed abundant synaptic specializations with neuronal elements in the host dentate gyrus. The predominant postsynaptic target (about 65% of all boutons) was dendritic shafts, whereas about 20% of the boutons contacted dendritic spines. Very few synapses onto neuronal perikarya were found in the grafted aged rats. In some of these cases, however, it was possible to identify the target as dentate granule cells. This situation is very similar to that seen in young control rats but significantly different than the distribution observed in the denervated young grafted group, where axosomatic contacts predominated. The results indicate that the graft-induced behavioral improvement seen in the aged rats may depend on the formation of functional cholinergic graft connections with neuronal elements in the host hippocampal formation.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Aging/physiology, Animals, Choline O-Acetyltransferase/metabolism, Cholinergic Fibers/ultrastructure, Female, Hippocampus/physiology, Learning Disorders/therapy, Memory Disorders/therapy, Rats, Rats, Inbred Strains, Septum Pellucidum/transplantation, Space Perception/physiology, Synapses/ultrastructure
in
Journal of Comparative Neurology
volume
252
issue
4
pages
10 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:0022996301
  • pmid:3782513
ISSN
0021-9967
DOI
10.1002/cne.902520405
language
English
LU publication?
no
id
6c4253e9-e0c2-4f5c-9b5a-fc932528c013
date added to LUP
2019-06-25 10:26:03
date last changed
2024-01-01 13:04:47
@article{6c4253e9-e0c2-4f5c-9b5a-fc932528c013,
  abstract     = {{<p>A group of aged, behaviorally impaired rats received suspension grafts of fetal septal-diagonal band tissue into the otherwise intact hippocampal formation. Three months after grafting, behaviorally recovered rats were studied by immunocytochemistry by using monoclonal antibodies to choline acetyltransferase (ChAT) and electron microscopy. The innervation of the host dentate gyrus by graft-derived ChAT-positive fibres was unmasked by acute removal of the intrinsic septal cholinergic innervation by fimbria-fornix transection 5-7 days before perfusion. The pattern of termination and ultrastructural connectivity were compared with previous results obtained from both young nonoperated control animals and a group of young rats with intrahippocampal septal grafts that had been subjected to denervation of the intrinsic cholinergic input at the time of transplantation. Graft-derived, ChAT-immunoreactive terminals formed abundant synaptic specializations with neuronal elements in the host dentate gyrus. The predominant postsynaptic target (about 65% of all boutons) was dendritic shafts, whereas about 20% of the boutons contacted dendritic spines. Very few synapses onto neuronal perikarya were found in the grafted aged rats. In some of these cases, however, it was possible to identify the target as dentate granule cells. This situation is very similar to that seen in young control rats but significantly different than the distribution observed in the denervated young grafted group, where axosomatic contacts predominated. The results indicate that the graft-induced behavioral improvement seen in the aged rats may depend on the formation of functional cholinergic graft connections with neuronal elements in the host hippocampal formation.</p>}},
  author       = {{Clarke, D J and Gage, F H and Nilsson, O G and Björklund, A}},
  issn         = {{0021-9967}},
  keywords     = {{Aging/physiology; Animals; Choline O-Acetyltransferase/metabolism; Cholinergic Fibers/ultrastructure; Female; Hippocampus/physiology; Learning Disorders/therapy; Memory Disorders/therapy; Rats; Rats, Inbred Strains; Septum Pellucidum/transplantation; Space Perception/physiology; Synapses/ultrastructure}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{4}},
  pages        = {{92--483}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Comparative Neurology}},
  title        = {{Grafted septal neurons form cholinergic synaptic connections in the dentate gyrus of behaviorally impaired aged rats}},
  url          = {{http://dx.doi.org/10.1002/cne.902520405}},
  doi          = {{10.1002/cne.902520405}},
  volume       = {{252}},
  year         = {{1986}},
}