The nucleus basalis magnocellularis cholinergic system: one hundred years of progress

The nucleus basalis magnocellularis (NBM) contains a population of large cholinergic (Ch) neurons that send their axons to the entire cortical mantle, the olfactory bulbs, and the amygdala. This is the centennial anniversary of the first exact description of this nucleus by Von Kölliker, who named it in honor of its discoverer. This review will focus upon recent attempts to understand the role of the NBM Ch neurons in higher cognitive function by the use of selective lesion analyses and electrophysiological recording techniques. Behavioral deficits associated with NBM lesions produced by injections of excitatory amino acid agonists have been demonstrated in a variety of tasks. Performance decrements produced by these lesions were initially interpreted as being the result of impairments in learning and memory abilities. However, the precise role of the Ch NBM neurons in these performance deficits could not be more thoroughly investigated until it became possible to produce selective and discrete lesions by injection of the immunotoxin, IgG-192 saporin. The results of investigations using this immunotoxin supported a role for NBM Ch neurons in the performance of tasks that require selected attentional abilities rather than learning and memory per se. These lesion analysis studies suggested that the corticopetal NBM Ch system may be involved in the control of shifting attention to potentially relevant, and brief, sensory stimuli that predict a biologically relevant event, such as a food reward. Electrophysiological evidence has implicated NBM Ch cells in the control of attentional processes, as well as a role in the control and maintenance of arousal and sleep states. Electrophysiological studies also suggest that NBM Ch neurons might influence cortical EEG activity in two ways, by its direct excitatory inputs and by an indirect inhibitory projection to the thalamic reticular nucleus. Taken together with the results of histological and anatomical studies of the basal forebrain, NBM Ch cells appear to be ideally located within the basal forebrain for evaluating sensory stimuli for their level of significance, via inputs from the midbrain and limbic system, and also to modulate intrinsic cortical responsiveness appropriately in order to attend to brief, highly salient sensory stimuli.