title: Attenuation of Responses to Self-Generated Sounds in Auditory Cortical Neurons.
abstract: Many of the sounds that we perceive are caused by our own actions, for example when speaking or moving, and must be distinguished from sounds caused by external events. Studies using macroscopic measurements of brain activity in human subjects have consistently shown that responses to self-generated sounds are attenuated in amplitude. However, the underlying manifestation of this phenomenon at the cellular level is not well understood. To address this, we recorded the activity of neurons in the auditory cortex of mice in response to sounds generated by their own behavior. We found that the responses of auditory cortical neurons to these self-generated sounds were consistently attenuated, compared with the same sounds generated independently of the animals' behavior. This effect was observed in both putative pyramidal neurons and in interneurons and was stronger in lower layers of auditory cortex. Downstream of the auditory cortex, we found that responses of hippocampal neurons to self-generated sounds were almost entirely suppressed. Responses to self-generated optogenetic stimulation of auditory thalamocortical terminals were also attenuated, suggesting a cortical contribution to this effect. Further analyses revealed that the attenuation of self-generated sounds was not simply due to the nonspecific effects of movement or behavioral state on auditory responsiveness. However, the strength of attenuation depended on the degree to which self-generated sounds were expected to occur, in a cell-type-specific manner. Together, these results reveal the cellular basis underlying attenuated responses to self-generated sounds and suggest that predictive processes contribute to this effect.
  
  
  
  Distinguishing self-generated from externally generated sensory input poses a fundamental problem for behaving organisms. Our study in mice shows for the first time that responses of auditory cortical neurons are attenuated to sounds generated manually by the animals' own behavior. This effect is distinct from the nonspecific effect of behavioral activity on auditory responsiveness that has previously been reported and its magnitude is modulated by the probability with which self-generated sounds occur, suggesting an underlying predictive process. We also reveal how this effect varies across cell types and cortical layers. These findings lay a foundation for studying impairments in the processing of self-generated sounds, which are observed in psychiatric illness, in animal disease models.
authors.affiliation: Institute of Neurophysiology, Neuroscience Center, Goethe University Frankfurt, Frankfurt am Main 60590, Germany.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Rummell
authors.affiliation: Institute of Neurophysiology, Neuroscience Center, Goethe University Frankfurt, Frankfurt am Main 60590, Germany.
authors.forename: Jan L
authors.initials: JL
authors.lastname: Klee
authors.affiliation: Institute of Neurophysiology, Neuroscience Center, Goethe University Frankfurt, Frankfurt am Main 60590, Germany sigurdsson@em.uni-frankfurt.de.
authors.forename: Torfi
authors.identifier: 0000-0002-0713-6408
authors.initials: T
authors.lastname: Sigurdsson
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D001303:Auditory Cortex / Q000502:physiology*; D001307:Auditory Perception / Q000502:physiology*; D001364:Awareness / Q000502:physiology; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology*; D012653:Self Stimulation / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology*
keywords: auditory cortex; corollary discharge; cortical layers; efference copy; mouse; sensory prediction