Changing spike duration can alter the firing pattern, as in the case of BK channels (Madison selleck compound and Nicoll, 1984 and Shao et al., 1999). Not only does the number of action potentials generated during a barrage of synaptic activities dictate the strength of the signal, the message conveyed also depends critically on the temporal pattern of spike firing. We have found that reducing CaCC activity could facilitate the EPSP-spike coupling, causing a short train of synaptic activities to transition from a single spike or no spike at all

to a burst of action potentials, indicating that CaCC modulation could adjust neuronal signaling both quantitatively and qualitatively. Action potentials can back-propagate into the dendrite of hippocampal pyramidal neurons (Hoffman et al., 1997 and Migliore et al., 1999). Modulation of the duration of

back-propagating action potential invading the dendritic tree is likely to have a strong impact not only on dendritic excitability, but also on coincidence detection buy Navitoclax of synaptic inputs—the basis of synaptic plasticity. The relative timing between an incoming synaptic potential and a back-propagating spike can determine whether the synapse giving rise to the synaptic potential is potentiated or depressed (Caporale and Dan, 2008 and Dan and Poo, 2004). A broader spike could conceivably widen the  time window during which a synaptic signal can be potentiated. This study provides

evidence for the involvement of Ca2+-activated Cl− channels in the negative feedback to rein in the excitatory synaptic responses. Remarkably, NFA block of CaCC increased synaptic potentials in a way similar to the apamin block of SK channels (Ngo-Anh et al., 2005). Reducing CaCC activity facilitates EPSP summation by leaving the earlier, smaller EPSP intact and most amplifying the later, larger EPSPs (Figure 6A; Table 1). This activity-dependent modulation is more nuanced than simple EPSP modulation and has two important implications (1) CaCC only reins in large EPSPs that have the potential of bringing the neuron to firing an action potential; CaCC acts as a brake, but not on all EPSPs. (2) Once CaCC is activated by Ca2+ influx through NMDA-Rs during a barrage of synaptic responses or Ca2+ from other cellular processes, the neuronal signaling outcome will be influenced by CaCC modulation of EPSP summation and the threshold for spike generation by EPSP. CaCC thus dynamically gates the information flow between neurons, and it only does so when there are sufficient neuronal activities to raise internal calcium level.