The basal forebrain is the major source of acetylcholine in the neocortex, and this projection has been variously described as either diffuse or highly specific. We used in vivo microdialysis to examine this discrepancy by collecting acetylcholine release simultaneously from visual, somatosensory and prefrontal cortical areas. Urethane-anesthetized rats were presented with visual and somatosensory stimulation in counter-balanced order and acetylcholine was measured using HPLC. Evoked acetylcholine release was modality-specific, i.e. visual stimulation evoked a large (75%) increase from visual cortex and little (24%) change from the somatosensory area whereas skin stimulation had the opposite effect. No increase was apparent in prefrontal cortex with either stimulation protocol. This experiment extends early studies using cortical cups to collect acetylcholine, and is consistent with the concept of functional specificity within the cholinergic basal forebrain with respect to both its sensory inputs and projections to the neocortex. This functional specificity within the cholinergic basal forebrain might be utilized in the modulation of different cortical regions during selective attention and plasticity.

To determine the sensitivity of basal forebrain cholinergic neurons to ionotropic glutamate receptor activation, acetylcholine was collected from the cerebral cortex of urethane-anesthetized rats using microdialysis while monitoring cortical electroencephalographic (EEG) activity. alpha-Amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA; 1, 10, or 100 muM), N-methyl-D-aspartate (NMDA; 100 or 1000 muM) or a combination of AMPA (10 muM) and NMDA (100 muM) was administered to the basal forebrain using reverse microdialysis. Both glutamate receptor agonists produced concentration-de pendent, several-fold increases in acetylcholine release indicating that they activated basal forebrain cholinergic neurons; AMPA was more potent, increasing acetylcholine release at a lower concentration than NMDA. The combination of AMPA and NMDA did not produce any greater release than each drug alone, indicating that the effects of these two drugs on cholinergic neurons are not additive. EEG was analyzed by fast Fourier transforms to determine the extent of physiological activation of the cortex. The highest concentrations of AMPA and NMDA tested produced small (25%) but significant increases in high frequency activity. There was a positive correlation across animals between the increases in power in the beta (14-30 Hz) and gamma (30-58 Hz) ranges and increases in acetylcholine release. These results indicate that glutamate can activate cholinergic basal forebrain neurons via both AMPA and NMDA ionotropic receptors but has a more modest effect on EEG activation. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.