The successful study of the cell biology of synaptic plasticity requires a tractable experimental model system. Ideally, such a model should consist of a defined population of identifiable neurons and be amenable to electrophysiological, genetic and molecular cell biological manipulations. A well-studied model system for studying plasticity in the adult vertebrate nervous system is the rodent hippocampus (). Critical for memory formation, the anatomy of the hippocampus renders it particularly suitable for electrophysiological investigation. It consists of three sequential synaptic pathways (perforant, mossy fiber and Schaffer collateral pathways), each with discrete cell body layers and axonal and dendritic projections (). Synaptic plasticity has been studied in all three hippocampal pathways in in vivo
and in vitro
preparations. Distinct stimuli elicit changes in synaptic efficacy; high frequency stimuli produce synaptic strengthening called long-term potentiation (LTP) and low frequency stimulation has been shown to produce synaptic weakening, called long-term depression (LTD). Further, different patterns of stimulation elicit changes in synaptic strength that persist over various time domains, with long-lasting forms, but not short-term forms, requiring new RNA and protein synthesis (1
Hippocampal plasticity can be studied in in vivo and in vitro preparations. Implanted electrodes can be used to stimulate and record from hippocampal pathways in living animals. The hippocampus can be dissected out of the brain and cut into 300–500 micron thick transverse slices that can be maintained and recorded from for hours (). Slices can also be kept as organotypic slice cultures for weeks, preserving many aspects of their architecture. Finally, hippocampal neurons can be studied in dissociated cultures, which are particularly amenable to manipulation and dynamic imaging of individual neurons and synapses. The development of genetically modified mice and vectors for acute manipulation of gene expression complete a rich tool-kit for studies of the cell and molecular biology of hippocampal synaptic plasticity.
This review focuses on long-lasting forms of plasticity that underlie learning and memory. We will consider, in turn, each component of the synapse: the presynaptic compartment, the postsynaptic compartment, and the synaptic cleft. In each case, we will discuss processes that undergo activity-dependent modifications to alter synaptic efficacy. Long-lasting changes in synaptic connectivity require new RNA and/or protein synthesis and so we then turn our attention to how gene expression is regulated within neurons. We will concentrate on studies of learning-related plasticity in the rodent hippocampus since these provide the most extensive evidence for the cell biological mechanisms of plasticity in the vertebrate brain. We will also limit our discussion to plastic changes at excitatory chemical synapses (though neurons also communicate at inhibitory and modulatory chemical synapses, and at electrical synapses, all of which show plasticity).