International Conference on Neural Signal Transduction in Health and Disease ‐ Cytokines, mitochondrial dysfunction and transport processes

Long-term processes of neuronal plasticity depend on signaling from the synapse to the nucleus and vice versa. Thus, long-term alterations of synaptic transmission as observed in cellular plasticity models like long-term potentiation (LTP) and long-term depression (LTD) are known to require de novo protein synthesis and gene transcription (Frey and Morris, 1998; Malenka, 2003; Thomas and Huganir, 2004). In particular induction of transcription is mediated by signaling pathways from the synapse to the nucleus (Deisseroth et al., 2003; West et al., 2002). The Ca ion is thought to act as one of the major mediators of synapto-nuclear signaling. Within this scheme a prevailing idea is the existence of Ca-microdomains coupled to the activation of synaptic NMDA receptors and transducing incoming Ca-events to downstream pathways (Hardingham et al., 2001; Blackstone and Sheng, 2002; Deisseroth et al., 2003). Although Ca exerts its signaling functions via interaction with a variety of Ca sensor proteins, pathways that result in a nuclear response to synaptic activity have primarily been based on signaling via calmodulin (CaM) (Deisseroth et al., 2003; West et al., 2002). In addition more recent concepts on other Ca-signaling processes involved in this scheme will be discussed.