AMPLIFICATION AND LINEARIZATION OF DISTAL SYNAPTIC INPUT TO CORTICAL PYRAMIDAL CELLS

1. Computer simulations were used to study the effect of voltage-dependent calcium and potassium conductances in the apical dendritic tree of a pyramidal cell on the synaptic efficacy of apical synaptic input. The apical tuft in layers 1 and 2 is the target of feedback projections from other cortical areas. 2. The current, I-soma, flowing into the soma in response to synaptic input was used to assess synaptic efficacy. This measure takes full account of all the relevant nonlinearities in the dendrites and can be used during spiking activity. I-soma emphasizes current flowing in response to synaptic input rather than synaptically induced voltage change. This measure also permits explicit characterization of the input-output relationship of the entire neuron by computing the relationship between presynaptic input and postsynaptic output frequency. 3. Simulations were based on two models. The first was a biophysically detailed 400-compartment model of a morphologically characterized layer 5 pyramidal cell from striate cortex of an adult cat. In this model eight voltage-dependent conductances were incorporated into the somatic membrane to provide the observed firing behavior of a regular spiking cell. The second model was a highly simplified three-compartment equivalent electrical circuit. 4. If the dendritic tree is entirely passive, excitatory synaptic input of the non-N-methyl-D-aspartate (non-NMDA) type to layers 1, 2, and 3 saturate at very moderate input rates, because of the high input impedance of the apical tuft. Layers 1 and 2 together can deliver only 0.25 nA current to the soma. This modest effect is surprising in view of the important afferents that synapse on the apical tuft and is inconsistent with experimental data indicating a more powerful effect. 5. We introduced in a controlled manner a voltage-dependent potassium conductance in the apical tuft, g(K), to prevent saturation of the synaptic response. This conductance was designed to linearize the relationship between presynaptic input frequency and the somatic current. We also introduced a voltage-dependent calcium conductance along the apical trunk, g(Ca) to amplify the apical signal, i.e., the synaptic current reaching the soma. 6. To arrive at a specific relationship between the presynaptic input rate and the somatic current delivered by the synaptic input, we derived the activation curves of g(K) and g(Ca) either analytically or numerically. The resultant voltage-dependent behavior of both conductances was similar to experimentally measured activation curves. 7. We propose that the apical tuft represents a separate integrative region that is coupled to the soma by a current amplifier in the apical dendrite. The gain of the amplifier can be controlled by modulating the properties of either g(Ca) or g(K).