EN
Immediate-early genes, c-fos in particular, are expressed in the brain upon neuronal activation. c-Fos expression is thought to reflect novelty detection and propensity for a plastic change as its levels decrease when the animal fully acquire a new task. However, its functional role in the brain remains largely unknown. In the present study, we used c-Fos immmunolabeling to identify the cortical network components within auditory and motor cortices that subserve sound frequency discrimination in a behavioral context. We designed a protocol in a fully automated cage for mice (IntelliCage), in which animals were supposed to discriminate between two sounds of different frequencies, one signaling safe access to water and another signaling punishment (air puff). c-Fos expression was analyzed at different stages of the training. Within the anterior parts of ventral and dorsal auditory cortices significant changes in c-Fos levels were observed that correlated with the discrimination learning. On the other hand, c-Fos expression in the motor cortex correlated only with motor activity. In order to address questions concerning the role of c-Fos in learning discrimination of sounds, associated with a particular behavioral meaning, RNA interference was used. c-Fos expression in the auditory cortex was blocked using short hairpin RNA (shRNA) delivered by lentiviral vectors. Mice were bilaterally injected with control vectors and harboring shRNA for c-fos (experimental). Then, the animals were subjected to sound discrimination training. Both the control and the experimental animals were responsive to the aversive cues, but the experimental group learnt much more slowly and showed faster extinction of the learned behavior than the control group. These results show the functional involvement of c-Fos within the auditory cortex in sound discrimination learning. More generally, they also support the idea that c-Fos marks neuronal plasticity rather than simple activation.