Equivalence of amplified current flowing from dendrite to soma measured by alteration of repetitive firing and by voltage clamp in layer 5 pyramidal neurons.

1. Plots of steady firing rate versus injected current (f-I relations) were constructed from intrasomatic injected current pulses applied alone (control relations) and together with dendritic glutamate iontophoresis (test relations) at sites on the distal apical dendrite 185-555 microns from the soma in layer 5 pyramidal neurons from rat cortex studied in a brain slice. The test f-I relations exhibited a parallel shift along the current axis, and the slopes of the control and test relations differed by < 10% in most neurons. This behavior indicates that constant injected current and steady glutaminergic dendritic input evoke equivalent steady-state repetitive firing in a neuron with active dendrites. The parallel shift of the f-I curves allowed us to compute the amplitude of axial current arriving in the soma from the apical dendrite during repetitive firing. 2. We compared the transmitted current computed from the f-I curve shift with that measured by somatic voltage clamp during the same iontophoresis. When measured during voltage clamp at different somatic membrane potentials, the transmitted current increased with somatic depolarization (was amplified) in most cells, an observation inconsistent with passive dendrites. This larger-amplitude current closely predicted the transmitted current computed from the f-I curve shift, whereas the smaller transmitted current measured at resting potential did not. A set of control experiments indicated that these different predictions were well within the measurement error associated with computation of transmitted current based on f-I curve shifts. The action of blocking agents confirmed that the depolarizing amplification depended on tetrodotoxin (TTX)- and D-2-amino-5-phosphonopentoic acid (APV)-sensitive dendritic channels. 3. The agreement of two independent measurements (somatic voltage clamp and f-I curve shift) of the axial current transmitted from dendrite to soma indicates that the amplification of transmitted current observed in voltage clamp occurs physiologically. We discuss the usefulness of the effective current concept for determining synaptic weighting in network models of neurons with active dendrites.