Metaplasticity, the adaptive changes of long-term potentiation (LTP) and long-term depression (LTD) in response to fluctuations in neural activity is well documented in visual cortex, where dark rearing shifts the frequency threshold for the induction of LTP and LTD. Here we studied metaplasticity affecting spike-timing-dependent plasticity, in which the polarity of plasticity is determined not by the stimulation frequency, butbythe temporal relationship between near-coincidental presynaptic and postsynapticfiring.Wefound that in mouse visual cortex the same regime of deprivation that restricts the frequency range for inducing rate-dependent LTD extends the integration window for inducing timing-dependent LTD, enabling LTD induction with random presynaptic and postsynaptic firing. Notably, the underlying mechanism for the changes in both rate-dependent and time-dependent LTD appears to be an increase of NR2b-containing NMDAR at the synapse. Thus, the rules of metaplasticity might manifest in opposite directions, depending on the plasticity-induction paradigms.
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