Diverse Effects of Arousal and Locomotion on Inhibitory and Excitatory Neurons in Auditory Cortex

Abstract

Cortical processing of sensory stimuli reflects a complex interplay between bottom-up sensory input and top-down modulatory effects of attention, arousal, and behavioral relevance. The mechanisms by which changes in brain states can modulate the activity of sensory neurons are not well understood. Recent evidence suggests that inhibitory interneurons form specific local circuits across cortical layers that allow them to reshape sensory-evoked responses and modulate spontaneous activity of cortical neurons. Recent advances in optogenetic and multineuronal recording technologies have made it possible to probe local inhibitory circuitry in auditory cortex to elucidate the involvement of VIP-expressing inhibitory cells during endogenous modulation by arousal and locomotion. Here, we describe the effects of endogenous modulatory signals and VIP activation on auditory cortical processing in different cell types and cortical layers. We find that both changes in behavioral state and VIP activation have diverse distributed effects on spontaneous and evoked activity of auditory neurons. Additionally, we show that some aspects of cortical modulation have cellular and layer specificity, although these specific effects do not necessarily overlap in their cellular targets. By separately examining the influence of artificial modulation by VIP activation and endogenous modulation by behavioral state, as well as their combined interactive effects, we conclude that running and arousal changes in auditory cortex are not mediated by VIP-expressing neurons. Finally, we discuss a different subclass of inhibitory interneurons, the main targets of VIP cells, and their known contributions to cortical modulation.