14 Synaptic Growth, Synaptic Maintenance, and the Persistence of Long-term Memory Storage

Abstract

The elementary events that underlie synaptic plasticity, the ability of neurons to modulate the strength of their synapses in response to extra-or intracellular cues, are thought to be fundamental both for the fine-tuning of synaptic connections during development, and for behavioral learning and memory storage in the adult organism. Indeed, activity-dependent modulation of synaptic strength and structure is emerging as one of the key mechanisms by which information is processed and stored within the brain (Kandel 2001).

Earlier behavioral studies in vertebrates and invertebrates have shown that the formation of both explicit (declarative) and implicit (non-declarative) forms of memory consist of two temporally distinct stages: short-term memory lasting minutes to hours and long-term memory lasting days, weeks, or longer. This temporal distinction in behavior is reflected in specific forms of synaptic plasticity that underlie each form of behavioral memory, as well as specific molecular requirements for each of these two forms of synaptic plasticity. In each case, the short-term form involves the covalent modifications of preexisting proteins mediated in part by cAMP and cAMP-dependent protein kinase (PKA) and is expressed as an alteration in the effectiveness of preexisting connections. In contrast, the long-term forms require PKA, MAPK, and CREB-mediated gene expression, new mRNA and protein synthesis, and are often associated with the growth of new synaptic connections (Bailey et al. 1996). For both implicit and explicit memory storage, the synaptic growth is thought to represent the final and self-sustaining change that stabilizes the long-term process. Initial insights into the molecular...