Synaptic Plasticity in vivo: More than Just Spike-Timing?

A commentary on Questions about STDP as a general model of synaptic plasticity. In their recent Perspective Article, Lisman and Spruston (2010) succinctly describe the crucial shortcomings of spike-timing-dependent plasticity (STDP) to serve as a unifying principle of synaptic plasticity. In particular, it is convincingly argued that postsynaptic depolarization rather than a somatic action potential (AP) is necessary and sufficient for the explanation of most results that have usually been interpreted within the STDP framework. I would like to add that we know even less about the importance of single backpropagating APs for synaptic plasticity in vivo. Direct evidence for STDP in vivo is limited and suffers from the fact that the used protocols significantly deviate, more often than not, from the traditional pairing of single pre-and postsynaptic spikes (Shulz and Jacob, 2010). Thus, many studies use long-lasting large-amplitude postsynaptic potentials (PSP), and pairing usually involves multiple postsynaptic spikes or high repetition rates. Our own experience from corti-co-striatal synaptic plasticity experiments indicates that classic STDP may be less effective in vivo than commonly expected (Schulz et al., 2010). A limited number of pairings (60 times) of cortical PSPs with a single current-induced postsynaptic AP at a slow rate (every 5 s) resulted in smaller and much more variable synaptic plastic changes than in previous in vitro studies that used com-On the other hand, we did find that regular somatic AP discharge during the pre-post pairings was necessary for any synaptic potentiation and that the direction of induced plasticity was crucially dependent on the relative timing of the synaptic inputs to the somatic AP on a millisecond-timescale (Schulz et al., 2010). This is strikingly different from previous in vitro studies that suggested that even large current-induced subthreshold depo-larizations are sufficient to induce synaptic changes at the cortico-striatal synapse over a wider range of timing intervals (Fino et al., 2009). These results demonstrate that one has to be very careful with extrapolating from in vitro results to the in vivo situation. Several factors have to be taken into account. First, most in vitro studies on STDP use cell cultures or acute slices from young animals, where neural circuits are naturally more plastic than in the adult brain (e.g., Meredith et al., 2003). While results obtained from such preparation are important for our understanding of developmental processes, their relevance to our concepts of learning is less clear. Second, the network state in vitro …