Cellular bases of neocortical activation: modulation of neural oscillations by the nucleus basalis and endogenous acetylcholine.
In the mammalian neocortex, the EEG reflects the state of behavioral arousal. The EEG undergoes a transformation, known as activation, during the transition from sleep to waking. Abundant evidence indicates the involvement of the neurotransmitter acetylcholine (ACh) in EEG activation; however, the cellular basis of this involvement remains unclear. We have used electrophysiological techniques with in vivo and in vitro preparations to demonstrate actions of endogenous ACh on neurons in auditory neocortex. In vivo stimulation of the nucleus basalis (NB), a primary source of neocortical ACh, (1) elicited EEG activation via cortical muscarinic receptors, (2) depolarized cortical neurons, and (3) produced a change in subthreshold membrane potential fluctuations from large-amplitude, slow (1-5 Hz) oscillations to low-amplitude, fast (20-40 Hz) oscillations. The NB-mediated change in pattern of membrane potential fluctuations resulted in a shift of spike discharge pattern from phasic to tonic. Stimulation of afferents in the in vitro neocortex elicited cholinergic actions on putative layer 5 pyramidal neurons. Acting via muscarinic receptors, endogenous ACh (1) reduced slow, rhythmic burst discharge and facilitated higher-frequency, single-spike discharge in burst-generating neurons, and (2) facilitated the appearance and magnitude of intrinsic membrane potential oscillations. These in vivo and in vitro observations suggest that neocortical activation results from muscarinic modulation of intrinsic neural oscillations and firing modes. Rhythmic-bursting pyramidal neurons in layer 5 may act as cortical pacemakers; if so, then modifying their discharge characteristics could alter local cortical networks. Larger, intercortical networks could also be modified, due to the widespread projections of NB neurons. Thus, NB cholinergic neurons may play a critical role in producing different states of neocortical function.
Department of Neuroscience, University of California, Riverside 92521.
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D000109:Acetylcholine / Q000502:physiology*; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001303:Auditory Cortex / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010830:Physostigmine / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013377:Substantia Innominata / Q000502:physiology*
D005971:Glutamates; D018698:Glutamic Acid; D001285:Atropine; D010830:Physostigmine; D000109:Acetylcholine