By Kameron Clayton

Our perception of the sensory world is so much more than a carbon copy of the physical energy that reaches our sense organs. “Internal state” variables such as expectation, recent stimulus histories and long-term auditory memories can powerfully shape what we hear and what meaning we take away from it. The pioneering neuroanatomist, Santiago Ramón y Cajal, postulated that the massive network of descending centrifugal projections originating in sensory regions of the cerebral cortex that innervate subcortical stages of sensory processing might play a role in this process, writing “What is the role of the centrifugal fibres? …do they transport some form of energy from the brain, the rapid accumulation of which in the sensory stations is necessary for the passage of ascending nerve currents?”

Layer 6 corticothalamic neurons in the auditory cortex of a behaving mouse recorded using two-photon calcium imaging.

The function of descending projection neurons that are found throughout the deepest layers of the sensory cortex have remained a mystery, owing to the difficulty of selectively targeting distinct types of feedback neurons during active sensing behaviors.  In recent work from the Polley lab, we addressed this question by performing targeted recordings from genetically identified neurons in layer 6 (L6) of the mouse auditory cortex that project to the thalamus (CT), We were able to monitor the activity of L6 CT neurons using a combination of two-photon calcium imaging and optogenetically “tagged” single-unit recordings while mice engaged in an active listening task. In this task, mice produced sound and received water rewards by contacting a spout with their tongue. This allowed us to ask whether this particular class of descending projection neuron was activated prior to movements that were expected to produce predictable sounds. We found that auditory L6 CTs showed large increases in their activity hundreds of milliseconds before the tongue contacted the spout, almost as if they were cells in a brain region that coordinated movement, rather than a typical sound processing cell in the auditory cortex. Consistent with this observation, we observed anatomical inputs to L6 CTs from the basal ganglia, a brain area involved in motor control.

What is the purpose of motor-related activity in L6 corticothalamic neurons? Among the most irrelevant sounds in a conversation is the sound of your own voice. As the L6 CTs increase their activity before movement, like a neuron you might find in motor cortex, auditory L6 CTs could suppress responses to sounds generated by our own movements. While it has been a century since Cajal described L6 CTs anatomically, our work provides a first step towards understanding how these cells contribute to integrative brain function and behavior.

Kameron Clayton is a graduate student in the lab of Daniel Polley at the Massachusetts Eye and Ear Infirmary.

Learn more in the original research article:
Clayton KK, Williamson RS, Hancock KE, et al. Auditory Corticothalamic Neurons Are Recruited by Motor Preparatory Inputs [published online ahead of print, 2020 Oct 28]. Curr Biol. 2020;S0960-9822(20)31531-1. doi:10.1016/j.cub.2020.10.027