The second scenario involves propagating pulses in an excitable network (Figure 9B). In this scenario, the excitatory connections need not reach as far, but the intermediate neurons (or at least some

of them) do need to fire for the wave to go further. Every wave that requires a regenerative process can be categorized in the second scenario. One way to discern among these scenarios is based on speed. Waves in the second scenario might propagate slower than in the first scenario, as activity may have to reverberate in a local group of neurons before it becomes strong enough to progress to the next location. This regeneration requires multiple synaptic delays and multiple stages of cellular integration, which all add to the delays imposed by axonal propagation. Examples of waves that are likely to follow the second scenario are the Up and Down oscillations seen when the cortex is in the synchronized state (Harris and selleck chemicals llc Thiele, 2011; Petersen et al., 2003b; Steriade et al., 1993). These oscillations travel markedly slower than axonal propagation, with a typical speed below 0.1 m/s. Consistent with

the second scenario, moreover, in these waves, activity spreads not only in subthreshold responses but also in suprathreshold spike responses. The importance of regenerative excitatory processes PD-1/PD-L1 inhibitor review in these slow waves is indicated by experiments in vitro, in which focal AMPA receptor blockers markedly slow down the waves (Compte and Wang, 2006; Golomb and Amitai, 1997; Pinto et al., 2005) or even stop the waves altogether (Sanchez-Vives and McCormick, 2000). In the first scenario, these manipulations could not have these effects. However, horizontal connections are still likely

to be involved, as network simulations suggest that they are crucial to reproduce these findings (Compte et al., 2003). The traveling waves elicited by a flashed bar in cat visual cortex, instead, seem to fall in the first scenario. Spike activity are largely and confined to the retinotopic region representing the stimulus (Bringuier et al., 1999) (see also Figure 4), so the wave sources are not regenerated in the neighboring regions. Rather, the waves appear to be caused by monosynaptic inputs from a single source and to propagate at the speed of axonal propagation. Indeed, we have seen that the wave speed measured in vivo (0.10–0.35 m/s) is consistent with the axonal propagation velocity measured in vitro (0.3 m/s, Hirsch and Gilbert, 1991). On the other hand, it is challenging to explain the context dependence of traveling waves (Figure 6) in the first scenario. Horizontal connections are present regardless of context, so it is not obvious that their effects would disappear in conditions of high overall contrast. A promising avenue of research in this respect concerns neuromodulators such as acetylcholine, which may play a role in determining the relative strength of thalamocortical inputs versus lateral inputs (Gil et al.