CONDITIONED AND UNCONDITIONED STIMULI INCREASE FRONTAL CORTICAL AND HIPPOCAMPAL ACETYLCHOLINE-RELEASE - EFFECTS OF NOVELTY, HABITUATION, AND FEAR

Recent evidence showing that basal forebrain cholinergic neurons with projections to the frontal cortex and hippocampus are activated by beh aviorally salient stimuli suggests that these neurons are involved in arousal and/or attentional processes. We sought in the present experim ents to test this hypothesis by examining whether unconditioned stimul i (a tone and flashing light) that normally increase cortical and hipp ocampal acetylcholine (ACh) release would fail to do so after habituat ion (i.e., repeated presentation with no programmed consequences). In addition, the extent to which presentation of these stimuli would cont inue to increase ACh release when they had previously been paired with an aversive stimulus was investigated. Three experimental groups were used: habituation, novel stimuli, and conditioned fear. Subjects in e ach of these groups were placed in a training apparatus for twelve 200 min sessions. While the habituation group received extensive exposure to the tone and light during the training sessions, subjects in the n ovel stimuli group were placed in the apparatus but were never exposed to the tone or light during these sessions. The conditioned fear grou p was treated identically to the habituation group, with the addition that the tone and light were paired with footshock. On completion of t hese training schedules, all animals were implanted with microdialysis probes in the frontal cortex and hippocampus. Two days later, they we re placed in the apparatus and the tone and light were presented to al l subjects during microdialysis. In the novel stimuli group, the tone and light (unconditioned stimuli) produced significant increases in fr ontal cortical and hippocampal ACh release. Similarly, in the conditio ned fear group, presentation of the tone and light (conditioned stimul i) also significantly increased ACh release in frontal cortex and hipp ocampus. In contrast, in the habituation group the tone and light fail ed to significantly enhance ACh release in either structure. During th e test session, the tone and light elicited a variety of arousal- and fear-related behaviors in the novel stimuli and conditioned fear group s. In contrast, subjects in the habituation group generally failed to respond to these stimuli. These data indicate that cortically and hipp ocampally projecting basal forebrain cholinergic neurons are activated by conditioned and unconditioned stimuli that produce arousal in rats (novelty or conditioned fear). In contrast, presentation of these sti muli to habituated animals fails to enhance ACh release. These finding s are consistent with a growing body of information indicating that AC h release in the cortex and hippocampus is reliably activated by behav iorally relevant stimuli. They also provide strong support for the hyp othesis that cholinergic neurons in the basal forebrain are involved i n arousal and/or attentional processes.