NORADRENERGIC MODULATION OF CHOLINERGIC NUCLEUS BASALIS NEURONS DEMONSTRATED BY IN-VITRO PHARMACOLOGICAL AND IMMUNOHISTOCHEMICAL EVIDENCE IN THE GUINEA-PIG BRAIN
P. Fort et al., NORADRENERGIC MODULATION OF CHOLINERGIC NUCLEUS BASALIS NEURONS DEMONSTRATED BY IN-VITRO PHARMACOLOGICAL AND IMMUNOHISTOCHEMICAL EVIDENCE IN THE GUINEA-PIG BRAIN, European journal of neuroscience, 7(7), 1995, pp. 1502-1511
The effects of noradrenalin were tested upon electrophysiologically ch
aracterized cholinergic nucleus basalis neurons in guinea-pig brain sl
ices. According to their previously established intrinsic membrane pro
perties, the cholinergic cells were distinguished by the presence of l
ow-threshold Ca2+ spikes and transient outward rectification that endo
wed them with the capacity to fire in low-threshold bursts in addition
to a stow tonic discharge. A subset of the electrophysiologically ide
ntified cholinergic cells that responded to noradrenalin had been fill
ed with biocytin (or biotinamide) and documented in previously publish
ed reports as choline acetyltransferase (ChAT)-immunoreactive. The nor
adrenalin-responsive, biocytin-filled/ChAT + cells were mapped in the
present study and shown to be distributed within the substantia innomi
nata amongst a large population of ChAT + cells. Slices from another s
ubset of noradrenalin-responsive, electrophysiologically identified ch
olinergic cells were stained for dopamine-beta-hydroxylase to visualiz
e the innervation of the biocytin-filled neurons by noradrenergic fibr
es. These biocytin-filled neurons were surrounded by a moderate plexus
of varicose noradrenergic fibres and were ostensibly contacted by a s
mall to moderate number of noradrenergic boutons abutting their soma a
nd dendrites. Applied in the bath, noradrenalin produced membrane depo
larization and a prolonged tonic spike discharge. This excitatory acti
on was associated with an increase in membrane input resistance, sugge
sting that it occurred through reduction of a K+ conductance. These ef
fects persisted when synaptic transmission was eliminated (by tetrodot
oxin or low Ca2+/high Mg2+) and were therefore clearly postsynaptic. T
he excitatory effect of noradrenalin was blocked by the alpha(1)-adren
ergic 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 m
ediation by an alpha(1)-adrenergic receptor. There was also evidence f
or a contribution by a beta-adrenergic receptor to the effect, since t
he beta-antagonist propranolol partially attenuated the effect of nora
drenalin, and the beta-agonist isoproterenol produced, like noradrenal
in, alone or when applied in the presence of the alpha(1)-antagonist p
razosin, membrane depolarization and an increase in tonic spike discha
rge. These results indicate that through a predominant action upon alp
ha(1)-adrenergic receptors, but with the additional participation of b
eta-adrenergic receptors, noradrenalin depolarizes and excites choline
rgic neurons. This action would tend to drive the cholinergic cells in
to a tonic mode of firing and to stimulate or increase the rate of rep
etitive spike discharge for prolonged periods. The noradrenergic locus
coeruleus neurons could thereby recruit the cholinergic basalis neuro
ns to act in tandem with them in facilitating cortical activation duri
ng wakefulness.