15 Control of Synaptic Function by Local Protein Synthesis and Degradation

Abstract

Synaptic plasticity—the dynamic modification of functional synaptic strength between neurons of the central nervous system—is generally believed to be a physical mechanism underlying learning and memory. An individual neuron in the mammalian CNS may contain up to 10,000 synaptic connections. Furthermore, small groups of synapses can be independently regulated: Synaptic enhancement induced at one location on the dendritic arbor does not spread throughout the entire arbor (Andersen et al. 1977; Bonhoeffer et al. 1989; Schuman and Madison 1994; Engert and Bonhoeffer 1999). The precision with which a neuron is able to fine-tune its synaptic inputs is likely related to the information-processing capacity of that individual cell. Without the ability to independently regulate its inputs, the neuron probably could not distinguish among the myriad inputs it receives. Although dendritic spines are highly dynamic postsynaptic structures, sometimes growing and shrinking in response to neuronal activity, the overall size and structure of a neuron are relatively fixed in the adult animal (Fiala et al. 2002; Harris et al. 2003). Rather than constantly growing new synapses, changes in synaptic strength are achieved through changing the complement and concentration of synaptic proteins, as well as modifying protein function by covalent modifications. The local concentration of synaptic proteins is influenced by many processes, including protein trafficking, buffering, and sequestration, as well as protein synthesis and degradation. For example, in the presynaptic compartment, rapid axonal transport can provide many of the proteins and vesicles required to maintain and modulate synaptic function. In addition, the calcium-binding...