, 2007, Roth and Häusser, 2001 and Schmidt-Hieber et al., 2007; Figures 4G and S4A) and number of branches (Figures S4C to S4D). In contrast, the distance-dependent decrease in both the simulated EPSC and qEPSC amplitudes were highly sensitive to changes in dendritic diameter (0.3 to 2 μm; Figures 4G and S4A). These simulations indicate that under somatic voltage-clamp conditions, poor space clamp of dendritic synaptic conductances can

account for a majority of the distance-dependent amplitude reduction and slowing of somatically recorded EPSCs. Similar results were obtained when simulating current-clamp recordings of EPSPs (Figures 4E and S4E) and Selleckchem GSK-3 inhibitor qEPSPs (Figures 4F and S4F), consistent with cable theory and previous experiments (Spruston et al., 1993, Thurbon et al., 1994 and Williams and Mitchell, 2008). Simulated EPSP and qEPSP exhibited a distance-dependent decrement in amplitude, although to a lesser extent than EPSCs (51% and 40%, respectively, at 47 μm) but were critically influenced by dendritic diameter (Figure 4H). The distance-dependent increase in the local depolarization was similar to that for voltage clamp. Taken together, these simulations demonstrate that passive neuron models with narrow dendritic diameters

AZD8055 ic50 are sufficient to mimic the observed distance-dependent decrease in qEPSC amplitude and slowing of its time course, and predict a dendritic gradient of filtered EPSPs. We next examined whether the large dendritic depolarization could decrease the synaptic current driving force and introduce a nonlinearity that would curtail linear summation of EPSPs within the same dendrite (Bloomfield et al., 1987 and Rall et al., 1967). We studied the subthreshold input-output relationship of single SC dendrites using rapid diffraction-limited one-photon photolysis. Photolysis-evoked EPSPs (pEPSPs) were elicited using a 405 nm and diode (Trigo et al., 2009) and laser

pulse durations between 30 and 100 μs in order to vary the amplitude of pEPSPs. Because of the high density of excitatory synapses (∼0.7 μm intersite distance; Figure 3E), pEPSPs could be evoked at most photolysis locations (Figure 5A). NMDARs were pharmacologically blocked since they are known to be extrasynaptic (Clark and Cull-Candy, 2002). We examined the input-output relationship by comparing the algebraic sum of individual pEPSPs from 5 laser locations (5 μm apart) along the dendrite, with compound pEPSPs in response to quasi-simultaneous (200 μs interval) activation of all 2 to 5 locations. The compound pEPSP were systematically smaller than the algebraic sum of its corresponding individual pEPSPs (Figures 5A and 5B). pEPSPs were converted to number of quanta by dividing them by the measured qEPSP of 2.5 mV (Supplemental Experimental Procedures).