The nucleus basalis and memory codes: auditory cortical plasticity and the induction of specific, associative behavioral memory.

Receptive field (RF) plasticity develops in the primary auditory cortex (ACx) when a tone conditioned stimulus (CS) becomes associated with an appetitive or aversive unconditioned stimulus (US). This prototypical stimulus-stimulus (S-S) association is accompanied by shifts of frequency tuning of neurons toward or to the frequency of the CS such that the area of best tuning of the CS frequency is increased in the tonotopic representation of the ACx. RF plasticity has all of the major characteristics of behavioral associative memory: it is highly specific, discriminative, rapidly induced, consolidates (becomes stronger and more specific over hours to days) and can be retained indefinitely (tested to two months). Substitution of nucleus basalis (NB) stimulation for a US induces the same associative RF plasticity, and this requires the engagement of muscarinic receptors in the ACx. Pairing a tone with NB stimulation actually induces specific, associative behavioral memory, as indexed by post-training frequency generalization gradients. The degree of acquired behavioral significance of sounds appears to be encoded by the number of neurons that become retuned in the ACx to that acoustic stimulus, the greater the importance, the greater the number of re-tuned cells. This memory code has recently been supported by direct neurobehavioral tests. In toto, these findings support the view that specific, learned auditory memory content is stored in the ACx, and further that this storage of information during learning and the instantiation of the memory code involves the engagement of the nucleus basalis and its release of acetylcholine into target structures, particularly the cerebral cortex.