Dendritic GABAB receptors control nonlinear information transfer along the dendro-somatic axis in layer 5 pyramidal neurons

Dendritic GABAB receptors (GABABRs) mediate a slow form of interhemispheric inhibition. Surprisingly, this inhibition has no detectable effect on the somatic membrane potential of layer 5 pyramidal neurons, whereas the action potential (AP) output is robustly decreased even when the input is proximal to the cell body. To elucidate the underlying mechanisms, we systematically mapped the AP frequency-current (F-I) relationship during dual patch-clamp recordings from soma and apical dendrite. The AP output function was governed by the synergistic interaction between dendritic and somatic compartments as the local input and transfer resistance from dendrite to soma (Kds) depended on the dendritic membrane potential. Thus, Kds doubled at an estimated rate of once per 28.7 mV depolarization due to HCN channel deactivation. In addition, dendritic L-type Ca2+ channels converted individual APs into dendritic Ca2+ spikes causing high-frequency bursts of APs (HFB) during large dendritic depolarization. Activation of dendritic GABABRs greatly reduced both nonlinear mechanisms. While direct block of L-type Ca2+ channels reduced the number of HFBs, K+ channel activation decreased voltage-dependent input and transfer resistances and decreased the AP rate under all conditions. These results highlight the powerful modulation of the input integration in pyramidal neurons by metabotropic receptor-activated K+ channels.