EFFECTS OF CHOLINERGIC DEAFFERENTATION AND NGF ON BRAIN ELECTRICAL COHERENCE

Rats received unilateral lesions of the nucleus basalis and were infus ed intracerebroventricularly (i.c.v.) over 3 weeks with nerve growth f actor (NGF) or vehicle. Electrocortical coherence was assessed at post operative days 4, 7, 14, and 21 from all possible pairs of eight epidu ral electrodes in the delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta-1 (12-20 Hz), and beta-2 (20-28 Hz) bands. On day 21 choline ace tyltransferase (ChAT) activity was measured in cortical tissue underly ing each electrode site. Lesions resulted in losses of interhemispheri c, as well as bilateral intrahemispheric coherence in the theta band ( F-1,F-21 = 28.61, p < 0.0001, F-1,F-21 = 4.30, p < 0.05), with no sign ificant differences seen in other bands. Changes were accentuated duri ng immobility compared with walking and exploratory behavior. Intrahem ispheric changes were greatest within the lesioned hemisphere (F-1,F-2 1 = 6.97, p < 0.01) in long connections between electrode pairings con necting frontal to posterior brain regions. Nerve growth factor (NGF) attenuated losses in ChAT (F-1,F-21 = 21.31, p < 0.0001) and intrahemi spheric coherence (F-1,F-21 = 9.66, p < 0.005), whereas interhemispher ic coherence showed no significant response. Intact animals receiving NGF showed increases in intrahemispheric coherence, as well as modest increases in ChAT. Increases in coherence in response to NGF occurred within 4-7 days following brain lesions, with no significant change du ring the 2 weeks thereafter. Our results suggest that coherence is sen sitive to cholinergic deafferentation, particularly of long corticocor tical connections. NGF differentially restores coherence within hemisp heres, as opposed to between hemispheres. Our study suggests that brai n function in Alzheimer's disease related to damage of transcallosal f iber tracts may not be responsive to cholinergic treatments. Future st udies may wish to evaluate the cognitive relevance of NGF's effects on intact brain. (C) 1998 Elsevier Science Inc.