UNIGE document Scientific Article
previous document  unige:10061  next document
add to browser collection
Title

Noradrenergic modulation of cholinergic nucleus basalis neurons demonstrated by in vitro pharmacological and immunohistochemical evidence in the guinea-pig brain

Authors
Fort, Patrice
Khateb, A.
Pegna, A.
Jones, B. E.
Published in European Journal of Neuroscience. 1995, vol. 7, no. 7, p. 1502-1511
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.
Keywords Adrenergic alpha-Agonists/pharmacologyAnimalsElectrophysiologyGuinea PigsImmunohistochemistryNerve Fibers/physiologyNeurons/drug effects/ physiologyNorepinephrine/pharmacology/ physiologyParasympathetic Nervous System/cytology/ physiologyReceptors, Adrenergic/physiologySubstantia Innominata/cytology/ physiology
Stable URL http://archive-ouverte.unige.ch/unige:10061
Full text
Identifiers
PMID: 7551176
Structures
156 hits and 0 download since 2010-08-06
Update
Export document
Format :
Citation style :