• adrenergic receptors;
  • guinea-pig;
  • low threshold Ca2+ spikes;
  • sleep;
  • substantia innominata


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-β-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 α1-adrenergic receptor antagonist prazosin and not by the α2-antagonist yohimbine, and it was mimicked by the α1-agonist L-phenylephrine but not by the α2-agonists clonidine and UK14.304, indicating mediation by an α1-adrenergic receptor. There was also evidence for a contribution by a β-adrenergic receptor to the effect, since the β-antagonist propranolol partially attenuated the effect of noradrenalin, and the β-agonist isoproterenol produced, like noradrenalin, alone or when applied in the presence of the α1-antagonist prazosin, membrane depolarization and an increase in tonic spike discharge. These results indicate that through a predominant action upon α1-adrenergic receptors, but with the additional participation of β-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. The noradrenergic locus coeruleus neurons could thereby recruit the cholinergic basalis neurons to act in tandem with them in facilitating cortical activation during wakefulness.