title: Ectopic noradrenergic hyperinnervation does not functionally compensate for neonatal forebrain acetylcholine lesion.
abstract: Adult rats who have undergone neonatal 192 IgG-saporin induced lesions of forebrain acetylcholine (ACH) neurons are normal on many behavioral tasks. In this study we determined whether ectopic hippocampal ingrowths, a documented consequence of these neonatal cholinergic lesions, functionally compensate for ACH denervation in these rats. Neonatal rats underwent systemic 6-hydroxydopamine (6-OHDA) injections on postnatal days (PND) 1-3 to prevent the ingrowths, and/or intraventricular 192 IgG-saporin injections on PND 7. The 192 IgG-saporin profoundly reduced basal forebrain p75 neurotrophin receptor (p75(NTR)) immunoreactive (IR) neurons. The 6-OHDA treatment abolished hippocampal and cortical dopamine-beta-hydroxylase (DBH) IR terminals, indicating the absence of normal norepinephrine (NE) innervation. Ectopic DBH IR and p75(NTR) IR varicosities which occurred in the hippocampus of 192 IgG-saporin treated rats were also eliminated by 6-OHDA treatment. Behavioral testing in adulthood indicated no effect of the treatments on the Morris water maze. 192 IgG-saporin treatment caused perseveration during delayed spatial alternation (DSA) and increased working but not reference memory errors on the radial arm maze (RAM). The 6-OHDA plus 192 IgG-saporin treated rats did not differ from the 192 IgG-saporin only rats on any task. These results indicate that ectopic hippocampal NE ingrowths do not functionally compensate for neonatal ACH lesions. Neonatal forebrain ACH lesion impairs working memory on the RAM but the absence of an effect on DSA contraindicates a basic dysfunction of short term memory. Despite severe combined neonatal loss of forebrain ACH and NE innervation, behavior is remarkably intact.
authors.affiliation: Institute of Neuroscience, Life Sciences Research Centre, Carleton University, Ontario, K1S 5B6, Ottawa, Canada. bpappas@ccs.carleton.ca
authors.forename: B A
authors.initials: BA
authors.lastname: Pappas
authors.forename: T
authors.initials: T
authors.lastname: Nguyen
authors.forename: B
authors.initials: B
authors.lastname: Brownlee
authors.forename: D
authors.initials: D
authors.lastname: Tanasoiu
authors.forename: T
authors.initials: T
authors.lastname: Fortin
authors.forename: N
authors.initials: N
authors.lastname: Sherren
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001522:Behavior, Animal / Q000502:physiology; D002452:Cell Count; D018678:Cholinergic Agents / Q000494:pharmacology; D003714:Denervation; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D000922:Immunotoxins / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D009699:N-Glycosyl Hydrolases; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000032:analysis; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013565:Sympatholytics
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D020800:Receptor, Nerve Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D013565:Sympatholytics; D016627:Oxidopamine; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine; D009638:Norepinephrine