Control of two-pathway signal integration in a model neocortical pyramidal cell

We demonstrate how neuromodulation and spatially targetted inhibition can alter the integration of the two streams of excitatory input in a thick-tufted layer 5 pyramidal cell, using a computational reduced-compartmental cell models. Choosing suitable ranges of brief current stimulus amplitudes, applied basally to either the soma or basal dendrites (basal stimulation) and to the apical tuft (apical stimulation) results in burst firing due to either stimulus alone, if strong enough, or by a combination of the stimuli at lower amplitudes. Applying tonic inhibition to the apical tuft removes the ability of apical input alone to generate a burst over the chosen amplitude range. A similar effect is achieved by reducing the tuft calcium channel conductance as an outcome of neuromodulation. Similarly, tonic inhibition to the basal dendrites removes the ability of basal stimulation alone to generate a burst, without blocking bursts resulting from apical calcium spikes. HCN channels in the apical dendrites may amplify or reduce bursting probability, depending on other active and passive properties of dendrites. So neuromodulation that decreases the conductance of these channels may act to reduce or increase bursting probability across the across the ranges of basal and apical inputs, depending on cell properties. These effects mimic those found previously by simply limiting the range of stimulus amplitudes (Graham et al., 2025) but now show that such changes in two-stream signal integration can happen through network inhibition and neuromodulation with no change in the excitatory driving stimulus strengths. These changes in signal integration also lead to changes in information transmitted by the cells bursting probability about the two input streams, as shown in Graham et al. (2025). Changes in cell morphology are also investigated by reducing the apical trunk length and are revealed to alter this two-stream signal integration through differential effects on passive and active interaction between the soma and apical tuft.