Selective lesion of cholinergic neurons in the medial septum by 192 IgG-saporin impairs learning in a delayed matching to position T-maze paradigm

This study examined whether selective destruction of cholinergic neurons in the medial septum impairs acquisition of a delayed matching-to-position (DMP) spatial memory task. Either the selective immunotoxin 192 IgG-saporin (SAP; 0.22 or 1.0 μg) or the non-selective excitatory neurotoxin ibotenate (...

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Veröffentlicht in:Brain research Jg. 943; H. 1; S. 132 - 141
Hauptverfasser: Johnson, David A, Zambon, Natalie J, Gibbs, Robert B
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Elsevier B.V 05.07.2002
Amsterdam Elsevier
New York, NY
Schlagworte:
Acetylcholine
Animals
Antibodies, Monoclonal - toxicity
Basal forebrain
Behavioral psychophysiology
Biological and medical sciences
Choline O-Acetyltransferase - metabolism
Cholinergic Fibers - drug effects
Cholinergic Fibers - physiology
Cognitive impairment
Fundamental and applied biological sciences. Psychology
Ibotenate
Immunotoxins - toxicity
Male
Maze Learning - drug effects
Maze Learning - physiology
N-Glycosyl Hydrolases
Neurotransmission and behavior
Prosencephalon - drug effects
Prosencephalon - physiology
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Rats
Rats, Sprague-Dawley
Ribosome Inactivating Proteins, Type 1
Saporins
Septal Nuclei - cytology
Septal Nuclei - drug effects
Septal Nuclei - physiology
Spatial memory
Basal forebrain
Acetylcholine
Ibotenate
Neurotransmitters, modulators, transporters, and receptors
Spatial memory
Cognitive impairment
Cholinergic neuron
Rat
Septum nucleus
Rodentia
Central nervous system
Vertebrata
Mammalia
Animal
Neurotransmitter
Lesion
Brain (vertebrata)
ISSN:0006-8993, 1872-6240
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Zusammenfassung:This study examined whether selective destruction of cholinergic neurons in the medial septum impairs acquisition of a delayed matching-to-position (DMP) spatial memory task. Either the selective immunotoxin 192 IgG-saporin (SAP; 0.22 or 1.0 μg) or the non-selective excitatory neurotoxin ibotenate (IBO; 5 μg), was infused directly into the medial septum of rats. Both doses of SAP, but not IBO, significantly impaired acquisition of the DMP task and blunted the initial alternating behavior of the rats in the T-maze. Histochemical staining revealed that both doses of SAP produced a near complete depletion of choline acetyltransferase (ChAT)-positive neurons in the medial septum. Some loss of parvalbumin staining was observed following administration of the higher dose, but not the lower dose, of SAP. In contrast, IBO produced a nearly complete depletion of parvalbumin-positive staining throughout the medial septum. IBO also produced a loss of ChAT-positive neurons and considerable local damage in the medial septum around the area of injection; however, many ChAT-positive neurons in the medial septum distal to the injection remained. A significant correlation between the number of days to reach criterion and ChAT activity in the frontal cortex and hippocampus was observed. The results suggest that low doses of SAP can be used to selectively destroy cholinergic neurons in the medial septum, and that selective destruction of these neurons significantly impairs acquisition of the DMP task. We propose that acquisition of the DMP task is a sensitive behavioral assay for the selective loss of basal forebrain cholinergic projections.
Bibliographie:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:0006-8993
1872-6240
DOI:10.1016/S0006-8993(02)02623-9