ABSTRACT
The synapse is a highly complex, finely tuned, and integrated signal transduction machine. The most heavily studied categories of signaling pathways engaged at the synapse are those that involve neurotransmitters and neurotrophic factors. Activation of such neurotransmitter and neurotrophic factor signaling pathways has been shown to play an important role in synaptogenesis (Martinez et al., 1998; Mattson, 1988), fast synaptic transmission (Edwards, 1995; Levine, Dreyfus, Black, & Plummer, 1995), long-term changes in synaptic function (Albensi & Mattson, 1999; Figurov, Pozzo-Miller, Olafsson, Wang, & Lu, 1996), synaptic degeneration/pruning (Mattson, 1988; Mattson, Keller, & Begley, 1998), and cell death (Mattson, 1988; Mattson & Furukawa, 1996; Oppenheim, 1991). It is well established that activity in neuronal circuits plays a major role in synaptic organization and programmed neuronal death during development of the nervous system and that synaptic signals involving neurotransmitters and neurotrophic factors are key mediators of activity-dependent neuronal plasticity (Purves, Snider, & Voyvodic, 1988). Programmed cell death in neurons, a form of apoptosis that occurs during development, appears to be controlled by synaptic signaling. Neurons that receive at least a threshold level of activation of neurotrophic factor receptors in presynaptic terminals survive, whereas neurons not receiving sufficient target-derived trophic factor undergo apoptosis. On the other hand, overactivation of glutamate receptors located in postsynaptic regions of dendrites may trigger neuronal death, particularly when levels of neurotrophic factors are low (see Mattson, 1996).
