MODIFICATION OF NEOCORTICAL ACETYLCHOLINE-RELEASE AND ELECTROENCEPHALOGRAM DESYNCHRONIZATION DUE TO BRAIN-STEM STIMULATION BY DRUGS APPLIEDTO THE BASAL FOREBRAIN

Acetylcholine released from the cerebral cortex was collected using mi crodialysis while stimulating the region of the pedunculopontine tegme ntum in urethane-anesthetized rats. Electrical stimulation in the form of short trains of pulses delivered once per minute produced a 350% i ncrease in acetylcholine release and a desynchronization of the electr oencephalogram, as measured by relative power in the 20-45 Hz range (l ow-voltage fast activity). Perfusion of the region of cholinergic neur ons believed to be responsible for the cortical release of acetylcholi ne, the nucleus basalis magnocellularis, was carried out using a secon d microdialysis probe. Exposure of the nucleus basalis magnocellularis to blockers of neural activity (tetrodotoxin or procaine) or to block ers of synaptic transmission (calcium-free solution plus magnesium or cobalt) produced a substantial decrease in the release of acetylcholin e and desynchronization evoked by brainstem stimulation. Exposure of t he nucleus basalis magnocellularis to the glutamate antagonist, kynure nate, resulted in a decrease in evoked acetylcholine release and elect roencephalogram desynchronization similar in magnitude to that produce d by nonspecific blockers, whereas application of muscarinic or nicoti nic cholinergic blockers to the nucleus basalis magnocellularis did no t reduce acetylcholine release or electroencephalogram desynchronizati on. Application of tetrodotoxin to the collection site in the cortex a bolished the stimulation-evoked acetylcholine release, but not the low baseline release indicating that cholinergic nucleus basalis magnocel lularis neurons have a low spontaneous firing rate in urethane-anesthe tized animals. The results of this study suggest that the major excita tory input to the cholinergic neurons of the nucleus basalis magnocell ularis from the pedunculopontine tegmentum is via glutamatergic and no t cholinergic synapses.