Auditory Corticothalamic Neurons Are Recruited by Motor Preparatory Inputs

• Published in: Current biology 2021-01, Vol.31 (2), p.310-321.e5
• Main Authors: Clayton, Kameron K., Williamson, Ross S., Hancock, Kenneth E., Tasaka, Gen-ichi, Mizrahi, Adi, Hackett, Troy A., Polley, Daniel B.
• Format: Article
• Language: English
• Subjects: Acoustic Stimulation; Animals; auditory cortex; Auditory Cortex - cytology; Auditory Cortex - physiology; Auditory Perception - physiology; cholinergic; corollary discharge; efference copy; FoxP2; Globus Pallidus - physiology; internal state; Intravital Microscopy; locomotion; Male; Mice; movement; Movement - physiology; Neural Pathways - physiology; Neurons - physiology; Optical Imaging; pallidocortical; Reward; sensorimotor integration; Stereotaxic Techniques; Thalamus - cytology; Thalamus - physiology
• ISSN: 0960-9822; 1879-0445; 1879-0445
• DOI: 10.1016/j.cub.2020.10.027

Corticothalamic (CT) neurons comprise the largest component of the descending sensory corticofugal pathway, but their contributions to brain function and behavior remain an unsolved mystery. To address the hypothesis that layer 6 (L6) CTs may be activated by extra-sensory inputs prior to anticipated sounds, we performed optogenetically targeted single-unit recordings and two-photon imaging of Ntsr1-Cre+ L6 CT neurons in the primary auditory cortex (A1) while mice were engaged in an active listening task. We found that L6 CTs and other L6 units began spiking hundreds of milliseconds prior to orofacial movements linked to sound presentation and reward, but not to other movements such as locomotion, which were not linked to an explicit behavioral task. Rabies tracing of monosynaptic inputs to A1 L6 CT neurons revealed a narrow strip of cholinergic and non-cholinergic projection neurons in the external globus pallidus, suggesting a potential source of motor-related input. These findings identify new pathways and local circuits for motor modulation of sound processing and suggest a new role for CT neurons in active sensing. [Display omitted] •L6 corticothalamic neurons (L6 CTs) were isolated during active listening tasks•L6 CT activity increases prior to movements that trigger sound and reward•Motor corollary input activates L6 CTs at similar latency to FS interneurons•Rabies tracing reveals monosynaptic inputs onto L6 CTs from globus pallidus Corticothalamic neurons (CTs) regulate excitability throughout the thalamocortical loop, but what regulates their excitability? Clayton et al. record from mouse auditory layer 6 CTs during active listening tasks. They find strong motor-related extra-sensory activation of layer 6 CTs beginning hundreds of milliseconds prior to movement onset.