4 μm dendritic diameter and membrane parameters matching experimental data (Rm = 20,000 Ωcm2 and Ri = 150 Ωcm), we calculated the steady-state dendritic length constant (λ) to be

365 μm (Equation S1; Supplemental Experimental Procedures), more than twice the average dendritic length (Sultan and Bower, 1998), suggesting that at steady-state SCs are electrically compact (Carter and Regehr, 2002 and Sultan and Bower, 1998). This was verified by estimating the reversal potentials of somatic and dendritic EPSCs which reversed in both cases near 0 mV (+4 and +6 mV, respectively; Figure S3). These data contrast with the +40 mV reversal potential of PC dendrites (Llano et al., 1991) and the +200 mV of pyramidal cell dendrites (Williams and Mitchell, 2008), confirming that SCs are electrotonically compact at steady state. In contrast, PI3K inhibitor rapid transient AMPAR conductances are expected to exhibit shorter length constants (Rall, SB431542 molecular weight 1967, Thurbon et al., 1994 and Williams and Mitchell, 2008).

We estimated that a 1 kHz sine wave would produce a λ < 50 μm in SCs, arguing that rapid AMPAR-mediated synaptic conductances may be heavily filtered even at short distances (Equation S2; Supplemental Experimental Procedures). To explore the impact of thin SC dendrites on AMPAR-mediated synaptic responses, we performed numerical simulations of voltage- and current-clamp using the neuron simulating environment (Hines and Carnevale, 1997) with an idealized SC morphology, where branch number and length

were matched to experimental values (Myoga et al., 2009), and the dendritic diameter was set to 0.4 μm (Figure 4B), since we did not observe significant tapering of dendritic widths (data not shown). This “average” SC morphology enabled the systematic examination of the influence of dendritic diameter, number of branch points and PSD scaling on SC dendritic integration. Rm and Ri were initially set to values indicated above, and the simulated synaptic conductance amplitude and time course were adjusted to match somatic EPSCs and qEPSCs (Figure 2). Simulated EPSCs (monitored at the soma) became smaller (Figures however 4C and S4C) and slower (Figure S4B) as synapse location was placed distally along the dendrite, consistent with experimental observations. This distance-dependent decrease in amplitude was associated with an increase in the local synaptic depolarization (Figures 4C and S4C). For example, a synapse located 47 μm away from the soma produced an EPSC 79% smaller than for a somatic synapse, while producing a 31 mV local dendritic depolarization. Simulated qEPSCs (Figures 4D and S4D) exhibited an amplitude decrease of 71% at 47 μm and were associated with an 8 mV local depolarization. When we scaled the dendritic synaptic conductance by 1.4 to match EM results (Figure 3F), the distance-dependent decrease in the simulated qEPSC amplitude (62% at 47 μm) matched more closely that of experimental qEPSC (52% at 47 μm; Figure 2).