This reduction in AP bursts was also apparent in the cumulative probability density function, yielding a significant difference in distribution (K-S test p < 0.01, Figure 8E). Taken together, these experiments show that Na+ currents in first nodes of Ranvier

facilitate the generation of high-frequency APs in the AIS. The present study demonstrates that the first node of Ranvier has a critical role in high-frequency selleck chemicals burst generation in L5 axons. Using direct and indirect approaches, including the analysis of axon length in slices, targeted axotomy, and nodal Na+ channel block at fluorescence-identified branchpoints, it was found that somatic depolarization near threshold recruits a persistent type of Na+ current from the first node of Ranvier.

In the population of burst firing L5 neurons, this nodal Na+ current hyperpolarizes the AP voltage threshold, selleck chemical amplifies the axosomatic AP ADP, and influences the input-output properties in the AIS by facilitating high-frequency spikes. High-frequency bursts are thought to encode specific information about sensory stimuli and greatly increase the reliability of synaptic transmission (de Kock et al., 2007, Kepecs et al., 2002, Lisman, 1997 and Williams and Stuart, 1999). About 40%–60% of the thick-tufted L5 neurons in the neocortex are prone to generate bursts both in vitro (Chagnac-Amitai et al., 1990, Franceschetti et al., 1995, Mason and Larkman, 1990 and Williams and

Stuart, 1999) and in vivo (de Kock and Sakmann, 2008). These neurons fire typically 2–6 APs independent of the type of input stimulus, suggesting specific intrinsic ion channel compositions or neuronal geometries. One cellular mechanism often implicated in burst generation is the slow regenerative feedback between back-propagating axosomatic Na+ APs and the calcium-mediated dendritic depolarization Dipeptidyl peptidase (Mainen and Sejnowski, 1996, Schwindt and Crill, 1999 and Williams and Stuart, 1999). Indeed, L5 neurons lacking large dendritic trees, such as the slender-type L5 neurons or thick-tufted L5 neurons, which are cut at the apical dendrite, switch from IB to RS patterns (Bekkers and Häusser, 2007 and Mason and Larkman, 1990). Whereas each Na+ AP is first initiated in the AIS (Foust et al., 2010, Khaliq and Raman, 2006, Monsivais et al., 2005, Palmer et al., 2010 and Palmer and Stuart, 2006; this study), three lines of evidence show that for the initiation of AP bursts, Na+ current flow from the first node is essential. First, IB firing was absent in L5 axons without a first branchpoint (Figure 2 and Figure 3); second, IB neurons lost the ability for high-frequency discharges after axotomy (Figure 4); and third, nodal Na+ channel block inhibited a significant fraction of the anterograde propagating axonal AP and abolished bursts (Figure 7 and Figure 8).