Dendritic excitability and neuronal morphology as determinants of synaptic efficacy.

The ability to trigger neuronal spiking activity is one of the most important functional characteristics of synaptic inputs and can be quantified as a measure of synaptic efficacy (SE). Using model neurons with both highly simplified and real morphological structures (from a single cylindrical dendrite to a hippocampal granule cell, CA1 pyramidal cell, spinal motoneuron, and retinal ganglion neurons) we found that SE of excitatory inputs decreases with the distance from the soma and active nonlinear properties of the dendrites can counterbalance this global effect of attenuation. This phenomenon is frequency dependent, with a more prominent gain in SE observed at lower levels of background input-output neuronal activity. In contrast, there are no significant differences in SE between passive and active dendrites under higher frequencies of background activity. The influence of the nonuniform distribution of active properties on SE is also more prominent at lower background frequencies. In models with real morphologies, the effect of active dendritic conductances becomes more dramatic and inverts the SE relationship between distal and proximal locations. In active dendrites, distal synapses have higher efficacy than that of proximal ones because of arising dendritic spiking in thin branches with high-input resistance. Lower levels of dendritic excitability can make SE independent of the distance from the soma. Although increasing dendritic excitability may boost SE of distal synapses in real neurons, it may actually reduce overall SE. The results are robust with respect to morphological variation and biophysical properties of the model neurons. The model of CA1 pyramidal cell with realistic distributions of dendritic conductances demonstrated important roles of hyperpolarization-activated (h-) current and A-type K(+) current in controlling the efficacy of single synaptic inputs and overall SE differently in basal and apical dendrites.