Cholinergic lesions by 192 IgG-saporin and short-term recognition memory: role of the septohippocampal projection.
Two experiments examined the effects of cholinergic basal forebrain lesions by intraventricular and intrahippocampal infusions of the immunotoxin 192 IgG-saporin on recognition memory in an operant delayed-non-matching-to-position task in rats. Intraventricular infusions produced extensive reductions in cortical and hippocampal choline acetyltransferase activity in the first experiment. Behaviourally, a mixed delay-dependent/independent accuracy deficit and increased biased responding was observed post-lesioning. Thus, both mnemonic as well as non-mnemonic processes were affected by the lesion. This performance deficit was indistinguishable from the impairment induced by acute intraventricular injections of the choline uptake inhibitor hemicholinium-3, which suggests that cholinergic damage induced by 192 IgG-saporin disrupted performance. In the second experiment more discrete intrahippocampal 192 IgG-saporin lesions were made, which reduced hippocampal choline acetyltransferase activity about 57%, although this reduction was not as extensive as following intraventricular injections. Although intrahippocampal lesions also impaired non-matching accuracy, this effect failed to reach significance during most stages of the experiment. Scopolamine just failed to significantly impair (P = 0.053) performance in hippocampal lesioned rats more than in controls. The nicotinic antagonist mecamylamine did not affect the lesion-induced changes in performance. These results suggest that the cholinergic basal forebrain, including the septohippocampal system, is important for the mediation of recognition memory, and muscarinic receptor-mediated mechanisms may be of greater importance than alterations of nicotinic receptor-mediated processes in the septohippocampal system.
Steckler
T
T
MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle-upon-Tyne, U.K.
Keith
A B
AB
Wiley
R G
RG
Sahgal
A
A
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000633:toxicity*; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000008:administration & dosage / Q000633:toxicity*; D003072:Cognition Disorders / Q000139:chemically induced*; D003216:Conditioning, Operant / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D000922:Immunotoxins / Q000008:administration & dosage / Q000633:toxicity*; D007267:Injections; D007276:Injections, Intraventricular; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D009699:N-Glycosyl Hydrolases; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D016548:Prosencephalon / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012601:Scopolamine / Q000494:pharmacology
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D012601:Scopolamine; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D005968:Glutamate Decarboxylase