State-dependent learning is a phenomenon in which the retrieval of newly ac
quired information is possible only if the subject is in the same sensory c
ontext and physiological state as during the encoding phase(1). In spite of
extensive behavioural and pharmacological characterization(2), no cellular
counterpart of this phenomenon has been reported, Here we describe a neuro
nal analogue of state-dependent learning in which cortical neurons show an
acetylcholine-dependent expression of an acetylcholine-induced functional p
lasticity. This was demonstrated on neurons of rat somatosensory 'barrel' c
ortex, whose tunings to the temporal frequency of whisker deflections were
modified by cellular conditioning. Pairing whisker stimulation with acetylc
holine applied iontophoretically yielded selective lasting modification of
responses, the expression of which depended on the presence of exogenous ac
etylcholine. Administration of acetylcholine during testing revealed freque
ncy-specific changes in response that were not expressed when tested withou
t acetylcholine or when the muscarinic antagonist, atropine, was applied co
ncomitantly, Our results suggest that both acquisition and recall can be co
ntrolled by the cortical release of acetylcholine.