Robustness of sensory-evoked excitation is increased by inhibitory inputs to distal apical tuft dendrites

Significance Even the simplest sensory stimulus activates millions of synapses across the cortex. How neurons integrate these highly specialized, but noisy synaptic input patterns to generate robust electrophysiological responses—that ultimately translate into behavior—remains elusive. Here, we provide first insight into a mechanism that may underlie the general phenomenon, observed across sensory modalities and species, that stimulation decreases variability in neuronal activity. Specifically, we show that during sensory stimulation, highly specialized inhibitory neurons provide synaptic input to distal dendrites of excitatory neurons, which reduces variability but not the mean amplitude of the response. Distal dendritic shunting may thus represent a general principle of cortex organization to ensure that noisy synaptic input patterns translate into robust sensory-evoked neuronal activity. Cortical inhibitory interneurons (INs) are subdivided into a variety of morphologically and functionally specialized cell types. How the respective specific properties translate into mechanisms that regulate sensory-evoked responses of pyramidal neurons (PNs) remains unknown. Here, we investigated how INs located in cortical layer 1 (L1) of rat barrel cortex affect whisker-evoked responses of L2 PNs. To do so we combined in vivo electrophysiology and morphological reconstructions with computational modeling. We show that whisker-evoked membrane depolarization in L2 PNs arises from highly specialized spatiotemporal synaptic input patterns. Temporally L1 INs and L2–5 PNs provide near synchronous synaptic input. Spatially synaptic contacts from L1 INs target distal apical tuft dendrites, whereas PNs primarily innervate basal and proximal apical dendrites. Simulations of such constrained synaptic input patterns predicted that inactivation of L1 INs increases trial-to-trial variability of whisker-evoked responses in L2 PNs. The in silico predictions were confirmed in vivo by L1-specific pharmacological manipulations. We present a mechanism—consistent with the theory of distal dendritic shunting—that can regulate the robustness of sensory-evoked responses in PNs without affecting response amplitude or latency.