title: Noradrenergic modulation of cholinergic nucleus basalis neurons demonstrated by in vitro pharmacological and immunohistochemical evidence in the guinea-pig brain.
abstract: The effects of noradrenalin were tested upon electrophysiologically characterized cholinergic nucleus basalis neurons in guinea-pig brain slices. According to their previously established intrinsic membrane properties, the cholinergic cells were distinguished by the presence of low-threshold Ca2+ spikes and transient outward rectification that endowed them with the capacity to fire in low-threshold bursts in addition to a slow tonic discharge. A subset of the electrophysiologically identified cholinergic cells that responded to noradrenalin had been filled with biocytin (or biotinamide) and documented in previously published reports as choline acetyltransferase (ChAT)-immunoreactive. The noradrenalin-responsive, biocytin-filled/ChAT+cells were mapped in the present study and shown to be distributed within the substantia innominata amongst a large population of ChAT+ cells. Slices from another subset of noradrenalin-responsive, electrophysiologically identified cholinergic cells were stained for dopamine-beta-hydroxylase to visualize the innervation of the biocytin-filled neurons by noradrenergic fibres. These biocytin-filled neurons were surrounded by a moderate plexus of varicose noradrenergic fibres and were ostensibly contacted by a small to moderate number of noradrenergic boutons abutting their soma and dendrites. Applied in the bath, noradrenalin produced membrane depolarization and a prolonged tonic spike discharge. This excitatory action was associated with an increase in membrane input resistance, suggesting that it occurred through reduction of a K+ conductance. These effects persisted when synaptic transmission was eliminated (by tetrodotoxin or low Ca2+/high Mg2+) and were therefore clearly postsynaptic. The excitatory effect of noradrenalin was blocked by the alpha 1-adrenergic receptor antagonist prazosin and not by the alpha 2-antagonist yohimbine, and it was mimicked by the alpha 1-agonist L-phenylephrine but not by the alpha 2-agonists clonidine and UK14.304, indicating mediation by an alpha 1-adrenergic receptor. There was also evidence for a contribution by a beta-adrenergic receptor to the effect, since the beta-antagonist propranolol partially attenuated the effect of noradrenalin, and the beta-agonist isoproterenol produced, like noradrenalin, alone or when applied in the presence of the alpha 1-antagonist prazosin, membrane depolarization and an increase in tonic spike discharge. These results indicate that through a predominant action upon alpha 1-adrenergic receptors, but with the additional participation of beta-adrenergic receptors, noradrenalin depolarizes and excites cholinergic neurons. This action would tend to drive the cholinergic cells into a tonic mode of firing and to stimulate or increase the rate of repetitive spike discharge for prolonged periods.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Département de Physiologie, Centre Médical Universitaire, Geneva 4, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Fort
authors.forename: A
authors.initials: A
authors.lastname: Khateb
authors.forename: A
authors.initials: A
authors.lastname: Pegna
authors.forename: M
authors.initials: M
authors.lastname: Mühlethaler
authors.forename: B E
authors.initials: BE
authors.lastname: Jones
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D006168:Guinea Pigs; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009412:Nerve Fibers / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D011941:Receptors, Adrenergic / Q000502:physiology; D013377:Substantia Innominata / Q000166:cytology / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D011941:Receptors, Adrenergic; D009638:Norepinephrine