Distinct depolarization patterns differentially regulate the slow- and fast-twitch properties of skeletal muscle fibers. We have used the fast quail Troponin I (TnIf) fast intronic regulatory element (FIRE), an enhancer necessary and sufficient to confer fast-muscle specificity, to identify cis- and trans-acting elements that regulate transcription of the TnIf gene in response to patterned motoneuron activity. To this end, adult skeletal muscles were transfected with TnIf FIRE-GFP reporter constructs to follow transcription in live myofibers stimulated with tonic, slow frequency or phasic, fast frequency patterned activity that mimic native "slow" and "fast" firing motoneuron activity. Interestingly, we find that slow stimulation patterns repress transcription from the TnIf FIRE, while fast patterned activity enhance its levels. These results indicate that TnIf expression is finely tuned by opposing activity-dependent mechanisms. We will report on a variety of experimental of approaches, which indicate that the calcineurin/NFAT-pathway, frequently reported to up-regulate transcription of genes expressed selectively in slow-twitch muscles, functions to downregulate transcription of the TnI FIRE in slow-twitch muscles. In contrast, we will show that a distinct element upregulates FIRE dependent transcription in response to fast-patterned activity; this element binds and is regulated by NF-kB. Consistent with our findings, NFAT and NF-kB are known to be calcium-regulated factors that differentially regulate downstream target genes in T-cells in response to distinct kinetics of calcium fluctuations. Our findings with TnI FIRE illustrate how excitable cells, like muscles and neurons, remain plastic throughout development.