Abstract
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.
| Original language | American English |
|---|---|
| Pages (from-to) | 310-321.e5 |
| Journal | Current Biology |
| Volume | 31 |
| Issue number | 2 |
| DOIs | |
| State | Published - 25 Jan 2021 |
Bibliographical note
Funding Information:We thank Evan Foss and Ishmael Stefanov for contributing to behavioral hardware development and Eyal Kimchi for guidance on using DeepLabCut. We thank D. Schneider for comments on an earlier version of the manuscript. We thank D. Kim and the Genetically Encoded Neuronal Indicator and Effector Project at the HHMI's Janelia Farm Research Campus for making the Thy1-GCaMP6s mouse publicly available. AAV5-Ef1a-DIO hChR2(E123T/T159C)-EYFP was developed by Karl Deisseroth. This work was supported by The Nancy Lurie Marks Family Foundation (D.B.P.); NIH grants DC017178 (D.B.P.), DC015388 (T.A.H.), and DC018327 (R.S.W.); NSF fellowship DGE1745303 (K.K.C.); and NIH fellowship DC015376 (R.S.W.). K.C.C. and R.S.W. performed all experiments and analyses on live animals with supervisory input from D.B.P. T.A.H. performed imaging and analysis of fixed tissue. G.T. and A.M. contributed the viral tracing reagents and technical oversight on their appropriate use. K.E.H. developed neurobehavioral software control. D.B.P. and K.K.C. wrote the manuscript with feedback from all authors. The authors declare no competing interests.
Funding Information:
We thank Evan Foss and Ishmael Stefanov for contributing to behavioral hardware development and Eyal Kimchi for guidance on using DeepLabCut. We thank D. Schneider for comments on an earlier version of the manuscript. We thank D. Kim and the Genetically Encoded Neuronal Indicator and Effector Project at the HHMI’s Janelia Farm Research Campus for making the Thy1-GCaMP6s mouse publicly available. AAV5-Ef1a-DIO hChR2(E123T/T159C)-EYFP was developed by Karl Deisseroth. This work was supported by The Nancy Lurie Marks Family Foundation (D.B.P.); NIH grants DC017178 (D.B.P.), DC015388 (T.A.H.), and DC018327 (R.S.W.); NSF fellowship DGE1745303 (K.K.C.); and NIH fellowship DC015376 (R.S.W.).
Publisher Copyright:
© 2020 Elsevier Inc.
Keywords
- FoxP2
- auditory cortex
- cholinergic
- corollary discharge
- efference copy
- internal state
- locomotion
- movement
- pallidocortical
- sensorimotor integration