Journal of Neuroscience, Vol 7, 742-752, Copyright © 1987 by Society for Neuroscience
Acetylcholine causes rapid nicotinic excitation in the medial habenular nucleus of guinea pig, in vitro
DA McCormick and DA Prince
The actions of ACh in the medial habenular nucleus (MHb) were investigated
using extra- and intracellular recording techniques in guinea pig thalamic
slice maintained in vitro. Applications of ACh to MHb neurons resulted in
rapid excitation followed by inhibition. Neither of these responses was
abolished by blockade of synaptic transmission, indicating that they are
consequences of ACh action directly on MHb cells. Local applications of the
nicotinic agonists nicotine and cytisine caused long-lasting excitation,
while applications of another nicotinic agonist, 1,1-dimethyl-4-
phenylpiperazinium caused both the excitatory and inhibitory responses.
Applications of the muscarinic agonists DL-muscarine and acetyl-beta-
methylcholine did not consistently cause either the excitatory or
inhibitory response. Adding the nicotinic antagonist hexamethonium to the
bathing medium blocked both the excitatory and inhibitory ACh responses,
while addition of the muscarinic antagonists atropine or scopolamine had no
effect. These results indicate that the effects of ACh on MHb neurons are
mediated by nicotinic receptors. Intracellular recordings revealed that ACh
or nicotine cause an increase in membrane conductance associated with
depolarizations that had an average reversal potential of -16 to -11 mV.
These results indicate that the ACh-induced excitation is due to an
increase in membrane cation conductance. The inhibitory response that
follows ACh-induced depolarization and repetitive firing was associated
with a hyperpolarization and an increase in membrane conductance. Similar
postexcitatory inhibition could also be elicited by direct depolarization
or by applications of glutamate, indicating that the hyperpolarizing
response to ACh may be an endogenous postexcitatory potential that is not
directly coupled to activation of nicotinic receptors. These results
suggest that cholinergic transmission in the MHb may be largely of the
nicotinic type. This nucleus may be of one of the major regions of the
nervous system through which nicotine mediates its central effects.
Previous Article | Next Article
