192-IGG-SAPORIN LESION OF BASAL FOREBRAIN CHOLINERGIC NEURONS IN NEONATAL RATS

Seven day old rats received bilateral intraventricular injections (200 ng) of the immunotoxin 192 IgG-saporin. When assayed in adulthood, th ese rats showed an 84% loss of hippocampal and a 52% loss of cortical choline acetyltransferase (ChAT) activity. ChAT was unaffected in the caudate. Cholinergic neurons immunoreactive (IR) for the low affinity neurotrophin receptor (p75(NTR)) were severely reduced throughout the basal forebrain nuclei. Cortical and hippocampal norepinephrine were i ncreased and these areas showed ingrowth of ectopic, p75(NTR) and dopa mine beta-hydoxylase IR varicosities. These were probably sympathetic axons. No obvious forebrain dysmorphogenesis was observed and cortical thickness was unaffected. These rats showed no evidence of impaired s patial learning/memory as assessed by the Morris water maze and delaye d spatial alternation, However, they were less active on the elevated plus apparatus and spent less time on the open arms, suggestive of inc reased timidity. 192 IgG-saporin appears to be a powerful tool to sele ctively lesion basal forebrain cholinergic neurons in the neonatal rat , Surprisingly, the neuromorphological and behavioral sequelae seem mi nimal. It may be necessary to achieve near-total neonatal destruction of forebrain cholinergic neurons before severe, lasting mnemonic effec ts are evident.