Effect of unilateral tympanotomy on auditory induced c-fos expression in cochlear nuclei.

The immediate early gene, c-fos, signals expression of target genes. Three natural occurring physiological entities: (1) learning, (2) plasticity, and (3) stress are proposed to use c-fos gene expression to signal molecular changes in neurons. The objective of this study was to determine whether c-fos expression is predominately activated by stress or by novel events associated with learning and plasticity. The approach was to quantitate the number of neurons in cochlear nuclei which express Fos protein following short-term novel sound stimuli together with either uni- or bilateral tympanotomy so as to differentiate novel sound stimuli from stress activation. The results show that routinely experienced sounds do not elicit c-fos expression in medullary cochlear nuclei, but novel sounds produced a 25-fold increase in the number of active cells. Following unilateral tympanotomy with novel sound stimulation, only a small number of cells were activated, ipsilaterally, (partially deafened side) while contralaterally, there was a 30-fold increase. After normalization of the data for control values, the data clearly indicate that novelty of sound stimuli induce c-fos gene expression. Furthermore, bilateral tympanotomy (bilateral partial deafening) with sound stimulation activated both sides by 20-fold, indicating that the c-fos response followed the sound stimulation. The data allow us to conclude that stress generates only a small contribution to c-fos gene expression while novel stimuli are potent signals, strongly implicating c-fos in novelty induced adaptation processes involved in learning and plasticity.