Long-term cortical plasticity evoked by electric stimulation and acetylcholine applied to the auditory cortex

Auditory fear conditioning with tone bursts followed by electric leg stimulation activates neurons not only in the auditory and somatosensory systems but also in many other regions of the brain and elicits shifts in the best frequencies (BFs) of collicular and cortical neurons, i.e., reorganization of the frequency (co-chleotopic) maps in the inferior colliculus and auditory cortex (AC). What are the neural elements minimally necessary for evoking long-term cortical BF shifts? We found that: (i) both electric stimulation and acetylcholine applied to the AC evoke the long-term cortical BF shift as does the conditioning; (ii) both electric stimulation of the AC and acetylcholine applied to the inferior colliculus increase the short-term collicular BF shift evoked by the cortical electric stimulation but do not change it into long-term; and (iii) as this short-term collicular BF shift is blocked by atropine, the development of the long-term cortical BF shift becomes slow and small. Therefore, the most essential neural elements for evoking the long-term cortical BF shift are the AC, corticofugal feedback and the cholinergic nucleus. Our current data support the Gao-Suga model, which hypothesizes that the small short-term cortical BF shifts are evoked by tonal stimuli without the association of conditioned and unconditioned stimuli in the multisensory thalamic nuclei and that these BF shifts are augmented and changed into the large long-term BF shifts by cholinergic neurons.