Selective immunolesioning of cholinergic neurons in nucleus basalis magnocellularis impairs prepulse inhibition of acoustic startle.
Information processing and attentional abnormalities are prominent in neuropsychiatric disorders. Since the cholinergic neurons located in the nucleus basalis magnocellularis have been shown to be involved in attentional performance and information processing, recent efforts to analyze the significance of the basal forebrain in the context of schizophrenia have focused on this nucleus and its projections to the cerebral cortex. We report here that bilateral selective immunolesioning of the cholinergic neurons in the nucleus basalis magnocellularis is followed by significant deficits in sensorimotor gating measured by prepulse inhibition of the startle reflex in adult rats. This behavioral approach is used in both humans and rodents and has been proposed as a valuable model contributing to the understanding of the neurobiological substrates of schizophrenia. The disruption of prepulse inhibition persisted over repeated testing. The selective lesions were induced by bilateral intraparenchymal infusions of 192 IgG saporin at a concentration having minimal diffusion into adjacent nuclei of the basal forebrain. The infusions were followed by extensive loss of choline acetyltransferase-immunopositive neurons. Our results show that the cholinergic neurons of the nucleus basalis magnocellularis represent a critical station of the startle gating circuitry and suggest that dysfunction of these neurons may result in impaired sensorimotor gating characteristic of schizophrenia.
Ballmaier
M
M
Department of Biomedical Sciences and Biotechnologies, Brescia University Mecial School, Italy. mballm@med.unibs.it
Casamenti
F
F
Zoli
M
M
Pepeu
G
G
Spano
P
P
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D020532:Basal Nucleus of Meynert / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000503:physiopathology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000494:pharmacology; D008297:Male; D009699:N-Glycosyl Hydrolases; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D002795:Choline O-Acetyltransferase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine