Activation and functional organization of the basal forebrain cholinergic system

The basal forebrain (BF) is the major source of cholinergic neurons projecting to the cerebral cortex. This thesis investigated two aspects of this cholinergic system: its excitability and the functional organization of its outputs.; Neurons are excited by different neurotransmitters, of which glutamate is the most important. Fast excitation is achieved through two types of ionotropic glutamate receptors called AMPA and NMDA receptors. The possible role of both AMPA and NMDA receptors in activating BF neurons and producing cortical EEG activation and ACh release was investigated. BF neurons were stimulated by administering various concentrations of AMPA, NMDA or both via a microdialysis probe. Cortical EEG was recorded and ACh release was collected from the somatosensory cortex via a microdialysis probe. Both AMPA and NMDA when delivered alone significantly increased cortical ACh release in a concentration-dependent manner; AMPA was more potent than NMDA. Both drugs produced cortical activation and the increases in high frequency activities (beta 2 and gamma) were positively correlated with evoked ACh release across individual animals. No additive or synergistic effects were observed on cortical ACh release or EEG activation when both drugs were given together.; The functional organization of the outputs of BF cholinergic neurons was investigated by stimulating visual and somatosensory pathways and measuring cortical ACh outflow from the visual, somatosensory and prefrontal cortices with microdialysis probes. Sensory stimulation evoked greater cortical ACh release from the cortical area associated with the sensory stimulation than in the two other cortical areas. These results support the existence of modality-specific BF cholinergic neurons.