Mechanism for a sliding synaptic modification threshold

Long-term potentiation (LTP) is a long-lasting increase in synaptic effectiveness that results from high frequency stimulation (HFS) of certain excitatory synapses in hippo-campus and neocortex (reviewed by Bliss and Colling-ridge, 1993). Because it is induced by brief episodes of electrical stimulation that resemble patterns observed in the brains of behaving animals, and because it can be very long-lasting, LTP has attracted a great deal of interest as a possible synaptic mechanism for learning and memory. In addition to this role, it has been suggested that the properties of LTP are also well-suited to account for aspects of experience-dependent development. LTP results when presynaptic activity coincides with strong post-synaptic depolarization beyond a threshold value. Thus, the development of binocularly responsive neurons in the visual cortex, for example, could be accounted for by asso-ciative LTP caused by the simultaneous activation of converging inputs from the two eyes. In addition to an LTP-like mechanism, it has been recognized for some time that, to account for developmental plasticity in the cortex, there must be a mechanism for activity-dependent decreases in synaptic strength. For example , during acritical period of early postnatal life, depriving an eye of visual patterns leads to an activity-dependent decrease in the effectiveness of deprived synapses in visual cortex. Indeed, the activity-dependent pruning of connections is a very prominent feature of postnatal development throughout the nervous system. Thus, developmental neurobiologists have sought an experimental model for use-dependent decreases in synaptic strength in the CNS. Here, theoretical analysis of developmental plasticity has been of considerable value. According to the Bienenstock-Cooper-Munro (BCM) theory developed to account for aspects of visual cortical development, long-term depression (LTD) should result when input activity consistently fails to activate postsynaptic neurons beyond the threshold for LTP (Bienenstock et al., 1982; Bear et al., 1987). This insight inspired the attempt to produce LTD with repetitive low frequency stimulation (LFS; Dudek and Bear, 1992). LFS-induced LTD is now a well-established model of synaptic plasticity in slices of hippo-campus and neocortex (reviewed by Bear and Malenka, 1994). In the CA1 region of hippocampus and in layer Ill of visual cortex, LFS of excitatory afferents produces LTD, and HFS produces LTP (Kirkwood et al., 1993). Both forms of synaptic plasticity depend on N-methyl-o-aspartate (NMDA) receptor activation and postsynaptic Ca " + entry. Available data support a model in which the state of correlation of pre-and postsynaptic aciiviiy is converted 5y the voltage-dependent …