, 2003). Thus, the PW may activate a fractionally higher number of synapses on proximal dendrites as compared to the SW (Lübke and Feldmeyer, 2007; Petreanu et al., 2009). For L2/3 pyramidal neurons of the visual cortex, it has been shown that STDP tends to induce lower levels of LTP in distal dendritic inputs (Froemke et al., 2005). This is possibly due to a strong attenuation of back-propagating APs toward distal dendrites (Sjöström et al., 2008), resulting in lower NMDAR activation levels in apical as compared to basal dendrites. In the barrel cortex such a mechanism could render SW-associated synapses less sensitive to STDP. Differences in clustering or functionality of synapses
may also cause contrasting levels of plasticity (Humeau et al., 2005), but it is as yet unclear if such differences exist between PW- and SW-associated inputs (Varga et al., 2011). Lateral or vertical forward inhibition (Adesnik and Scanziani, selleck screening library 2010; Chittajallu and Isaac, 2010; House et al., 2011; Kimura et al., 2010; Swadlow and Gusev, 2002) could further sculpt the differences between PW- and SW-associated excitatory pathways. In our study the inhibitory/excitatory conductance ratio was slightly but significantly higher for SW-evoked responses as compared to PW-evoked responses (Figures 6 and 7). In addition the inhibitory currents preceded on average the excitatory currents
for the SW, whereas find more for the PW the inhibitory currents occurred after excitation. This prompts the speculation that the SW recruits a different or an additional and slightly more potent inhibitory PAK6 circuit, which may efficiently constrain the temporal summation of EPSPs (Pouille and Scanziani, 2001) or shunt back-propagating APs (Tsubokawa and Ross, 1996) and contribute to the insensitivity to forms of plasticity. In support of this we found that a block of GABAergic inputs greatly facilitated SW-driven STD-LTP (Figure 8).
Altogether, it is likely that differences in both excitatory and inhibitory pathways render the SW-associated inputs less permissive to STD-LTP than the PW-associated synapses. We showed that trimming of all except two neighboring whiskers facilitated the induction of SW-driven STD-LTP (Figure 5). This is in line with an ex vivo study in which across-barrel STD-LTP was facilitated after deprivation (Hardingham et al., 2011). Whisker trimming did not change the baseline levels of SW- and PW-evoked responses at the population level. However, the average SW/PW ratio had increased for most cells (Figure 4). Because the recorded neurons were current clamped above the inhibitory reversal potential (Ei = −100mV), this could have been caused by a reduction in SW-associated inhibition (Kelly et al., 1999). Alternatively, excitatory synapses from surround inputs could have been potentiated (Glazewski et al., 2000). Interestingly, DWE did not block or occlude STD-LTP for either the PW or SW.