Ectopic noradrenergic hyperinnervation does not functionally compensate for neonatal forebrain acetylcholine lesion

Adult rats who have undergone neonatal 192 IgG-saporin induced lesions of f orebrain acetylcholine (ACH) neurons are normal on many behavioral tasks. I n this study we determined whether ectopic hippocampal ingrowths, a documen ted consequence of these neonatal cholinergic lesions, functionally compens ate for ACH denervation in these rats. Neonatal rats underwent systemic 6-h ydroxydopamine (6-OHDA) injections on postnatal days (PND) 1-3 to prevent t he ingrowths, and/or intraventricular 192 IgG-saporin injections on PND 7. The 192 IgG-saporin profoundly reduced basal forebrain p75 neurotrophin rec eptor (p75(NTR)) immunoreactive (IR) neurons. The 6-OHDA treatment abolishe d hippocampal and conical dopamine-beta-hydroxylase (DBH) IR terminals, ind icating the absence of normal norepinephrine (NE) innervation. Ectopic DBH IR and p75NTR IR varicosities which occurred in the hippocampus of 192 IgG- saporin treated rats were also eliminated by 6-OHDA treatment. Behavioral t esting in adulthood indicated no effect of the treatments on the Morris wat er maze. 192 IgG-saporin treatment caused perseveration during delayed spat ial 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 resul ts indicate that ectopic hippocampal NE ingrowths do not functionally compe nsate for neonatal ACH lesions. Neonatal forebrain ACH lesion impairs worki ng memory on the RAM but the absence of an effect on I)SA contraindicates a basic dysfunction of short term memory. Despite severe combined neonatal l oss of forebrain ACH and NE innervation, behavior is remarkably intact. (C) 2000 Elsevier Science B.V. All rights reserved.