If local boosting at the dendritic site compensates the loss of driving force completely, then EPSPΔ• must be equal in magnitude to EPSP•. This was the case for control conditions with synapses incorporating both AMPA and NMDA receptors (Figure 9A, lower traces), but not for synapses containing only AMPA receptors (EPSPΔ• smaller than EPSP•, Figure 9B, lowermost traces). These modeling data are consistent with the physiological data and indicate that the loss of local driving force in granule cell dendrites can be compensated by voltage-dependent

boosting. Figures 9C and 9D depict the corresponding voltage recordings from the model cell soma. At the soma, EPSPΔ• was considerably larger than the EPSP• (Figure 9C), consistent with the gain seen in physiological experiments (Figures 7D and 7E) and modeling experiments (not shown). Since the stimulation of sum EPSPs is slightly asynchronous in this model (Δt of 1.1 ms between every individual Screening Library high throughput stimulation, consistent with the experimental paradigm), propagation of these voltage transients benefits from the

frequency-dependent transfer Z-VAD-FMK supplier properties of granule cell dendrites described in detail in Figure 5 and Figure 6. In summary, the total linear gain seen in the somatic compartment is caused first by a local boosting that is dependent on NMDA receptors, Na+ and Ca2+ channels, and a subsequent propagation effect that favors slightly asynchronous sum EPSPs over single spine EPSPs (Figure 9E). These properties cause granule cell integration to be relatively independent of input synchrony. This behavior is qualitatively different from CA1 pyramidal neurons, in which input synchrony profoundly influences dendritic integration (see Figures 7F–7I, and Losonczy and Magee, 2006). In pyramidal neurons, individual dendritic branches can exhibit specific forms of integration that differ markedly between adjacent branches

(Losonczy and Magee, 2006 and Remy et al., 2009). Carnitine dehydrogenase We studied how inputs on different dendritic subbranches interact in dentate granule cells by selecting four sets of seven spines on two daughter branches emanating from the same parent dendrite (Figure 10A). We then stimulated sets of seven spines to obtain the corresponding gluEPSPs (1A, 1B, 2A, and 2B, Figure 10B). Subsequently, we stimulated various combinations of seven spine sets (1A+1B, 2A+2B, 1B+2A and 2B+1A, black traces in Figure 10B). We compared these measured EPSPs with the EPSPs expected from arithmetic summation of the gluEPSPs derived from stimulation of seven spine sets (gray traces in Figure 10B). Determining the ratio of measured and calculated compound gluEPSPs to stimulation of 14 spines situated either on one or two different branches revealed that the spatial distribution of inputs does not appear to affect integration in granule cells (Figure 10D, GC, n.s., Wilcoxon rank test).