Spatially targeted inhibitory rhythms differentially affect neuronal integration

Pyramidal neurons form dense recurrently connected networks with multiple types of inhibitory interneurons. A major differentiator between interneuron subtypes is whether they synapse onto perisomatic or dendritic regions. They can also engender local inhibitory rhythms, beta (12-35 Hz) and gamma (40-80 Hz). The interaction between the rhythmicity of inhibition and its spatial targeting on the neuron may determine how it regulates neuronal integration. Thus, we sought to understand how rhythmic perisomatic and distal dendritic inhibition impacted integration in a layer 5 pyramidal neuron model with realistic dendrites supporting Na⁺, NMDA, and Ca²⁺ spikes. We found that inhibition regulated the coupling between dendritic spikes and action potentials in a location and rhythm-dependent manner. Perisomatic inhibition principally regulated action potential generation, while distal dendritic inhibition regulated the incidence of dendritic spikes and their temporal coupling with action potentials. Perisomatic inhibition was most effective when provided at gamma frequencies, while distal dendritic inhibition functioned best at beta. Moreover, beta modulated responsiveness to distal inputs in a phase-dependent manner, while gamma did so for proximal inputs. These results may provide a functional interpretation for the reported association of soma-targeting parvalbumin-positive interneurons with gamma and dendrite-targeting somatostatin interneurons with beta.