, 1997). This dependence was characterized in detail by Bi and Poo (1998) and named “spike-timing-dependent plasticity” (STDP) by Song et al. (2000). In canonical STDP, LTP occurs when presynaptic spikes (and associated EPSPs) lead postsynaptic spikes by up to ∼20 ms, and LTD occurs when postsynaptic spikes lead presynaptic spikes and EPSPs by up to 20–100 ms, with a sharp (1–5 ms) transition between LTP and LTD (Markram et al., 1997; Bi and Poo, 1998; Celikel et al.,

2004) (Figure 1). Plasticity buy Icotinib requires multiple (typically 60–100) pre-post spike pairs. This is termed “Hebbian” STDP because it strengthens synaptic inputs that lead (and therefore contribute to) postsynaptic firing and depresses inputs that are uncorrelated with postsynaptic spikes. Not all STDP is alike, however. LTD in a cerebellum-like structure in the electric fish was also discovered in 1997 to be tightly spike-timing dependent, but in this case pre-leading-post spike order drove LTD (Bell et al., 1997), similar to anti-Hebbian LTD at the parallel fiber-Purkinje cell synapse in mammalian cerebellum. Thus, spike timing governs multiple forms of plasticity. STDP has now been observed at >20 different types of synapses from insects to mammals, and from striatum to neocortex. Its cellular basis

is increasingly understood. It is widely utilized in computational models of neural network plasticity and learning, and its apparent simplicity has led some to propose that it is a universal “first rule” or kernel for

PF-01367338 mw associative plasticity. However, this view is oversimplified. Early studies recognized that spike timing is only one of several factors, including firing rate and dendritic depolarization, within a multifactor plasticity rule (Markram et al., 1997; Sjöström et al., 2001). The relevance of spike timing varies across synapses, with strong spike-timing dependence (i.e., classical STDP) being restricted to specific dendritic zones and activity regimes. This review summarizes our understanding of STDP and evaluates Megestrol Acetate in detail the relative importance of spike timing versus other factors for plasticity in vitro and in vivo. Many excellent reviews have been published on STDP (e.g., Abbott and Nelson, 2000; Dan and Poo, 2006; Letzkus et al., 2007; Caporale and Dan, 2008; Sjöström et al., 2008; Froemke et al., 2010a), including a comprehensive history (Markram et al., 2011). Canonical STDP is bidirectional and order-dependent, with pre-leading-post spiking driving LTP, and post-leading-pre spiking driving LTD. It also has precise temporal windows for LTP and LTD (10 to ∼100 ms time scale) ( Markram et al., 1997; Bi and Poo, 1998). This original definition has expanded to include other plasticity that depends on spike timing, but is not bidirectional or order-dependent (e.g.