The Return of the Spike Postsynaptic Action Potentials and the Induction of LTP and LTD

mark where postsynaptic spiking was concerned. Perhaps the most quoted idea in the history of neurosci-The Last Laugh ence is the synaptic modification postulate proposed Recently, an exciting set of experiments have caused by the Canadian psychologist Donald Hebb in his 1949 renewed interest in postsynaptic spiking and synaptic book, The Organization of Behavior. Formulated to ex-plasticity and have refocused attention on the literal plain how memories could be stored as alterations in interpretation of Hebb's postulate. The basic obser-synaptic strength, it reads: vation that sparked this new era was the conclusive When an axon of cell A is near enough to excite a cell demonstration (with simultaneous whole-cell patch recording at axonal, somatic, and dendritic loci on a single B and repeatedly or persistently takes part in firing it, neuron) that Na ϩ spikes initiated at the axon hillock some growth process or metabolic change takes can backpropagate into the dendritic arbor (reviewed place in one or both cells such that A's efficiency, as by Stuart et al., 1997b). This propagation is active. It is one of the cells firing B, is increased. mediated and modulated by the activity of dendritic While this proposal generated a certain amount of voltage-gated ion channels. Most importantly, the back-interest upon its publication, it wasn't until 1973, when propagating spike provides a signal capable of in-Bliss and Lomo first reported the phenomenon of long-forming the synapse that the postsynaptic cell has fired. term potentiation (LTP) in the hippocampus, that a trac-Very recently, this technique has been used to conclu-table electrophysiological model system emerged that sively demonstrate that stimulation of excitatory syn-could be used to study use-dependent alteration of syn-apses can result in local Na ϩ spikes in the dendrite, an aptic strength in the mammalian brain and that appeared idea that had been suggested by classic field potential to embody the Hebb postulate (Wigströ m et al., 1988). LTP is a persistent increase in synaptic strength that is Sakata, 1962) and intracellular (Spencer and Kandel, typically produced by brief high-frequency stimulation 1961) recordings. Recordings made from neocortical of presynaptic neurons. In its most commonly studied layer 5 pyramidal neurons (Stuart et al., 1997a) and hip-form, it requires activation of postsynaptic NMDA recep-pocampal CA1 pyramidal neurons (Golding and Sprus-tors and consequent Ca 2ϩ influx. Phenomenologically, it ton, 1998) have shown that sufficiently strong synaptic appears to obey the Hebb postulate: neither presynaptic stimulation can …