Scientific Understanding of Consciousness
Auditory Cortical Processing Modulated by Movement
Nature 513, 189–194 (11 September 2014)
A synaptic and circuit basis for corollary discharge in the auditory cortex
David M. Schneider, et.al.
Department of Neurobiology, Duke University School of Medicine, Durham, North Carolina 27710, USA
Sensory regions of the brain integrate environmental cues with copies of motor-related signals important for imminent and ongoing movements. In mammals, signals propagating from the motor cortex to the auditory cortex are thought to have a critical role in normal hearing and behaviour, yet the synaptic and circuit mechanisms by which these motor-related signals influence auditory cortical activity remain poorly understood. Using in vivo intracellular recordings in behaving mice, we find that excitatory neurons in the auditory cortex are suppressed before and during movement, owing in part to increased activity of local parvalbumin-positive interneurons. Electrophysiology and optogenetic gain- and loss-of-function experiments reveal that motor-related changes in auditory cortical dynamics are driven by a subset of neurons in the secondary motor cortex that innervate the auditory cortex and are active during movement. These findings provide a synaptic and circuit basis for the motor-related corollary discharge hypothesized to facilitate hearing and auditory-guided behaviours.
In a wide variety of sensory systems, including the auditory system, copies of motor signals (that is, corollary discharge signals) are used to modulate sensory processing in a movement-dependent manner In humans, evidence of this motor influence includes modulation of auditory cortical activity during vocalization and music-related manual gestures. More broadly, corollary discharge signals are theorized to facilitate hearing during acoustic behaviours, to convey predictive signals important for complex forms of motor learning, such as speech and music, and to drive auditory hallucinations in certain pathological states.
While motor-related signals are likely to influence auditory processing at many sites in the brain, those operating at cortical levels are apt to be especially important to learning acoustic behaviours and generating auditory hallucinations. Although the synaptic and circuit origins of corollary discharge signals in the auditory cortex remain enigmatic, a direct projection from the motor cortex to the auditory cortex is a common feature of the mammalian brain, providing a substrate for conveying corollary discharge signals to the auditory cortex. Moreover, heightened motor cortical activity correlates with auditory cortical suppression in humans22, and activating motor cortical synapses in the auditory cortex suppresses tone-evoked auditory cortical responses in the anaesthetized mouse.
Despite the widespread observation that movement can modulate auditory cortical activity and the presumed role of the motor cortex in driving this modulation, the synaptic and circuit mechanisms by which the motor cortex influences auditory cortical activity during movement remain unresolved. Identifying these mechanisms requires integrating high-resolution electrophysiology techniques with circuit dissection strategies in freely behaving animals to establish causal links among synapses, circuits and behaviour. Here we combine in vivo intracellular physiology with optogenetic circuit manipulations in freely behaving mice to identify a synaptic signature of movement in the auditory cortex and to elucidate local and long-range circuits that modulate auditory cortical activity during movement.
What is the source of motor-related signals in the auditory cortex? Anatomical tracing studies in the mouse show that the auditory cortex receives input from several motor-related regions, including the cingulate cortex, primary motor cortex, and secondary motor cortex (M2), the last of which when optogenetically activated can drive strong feedforward inhibition in the auditory cortex mediated in part by PV+ interneurons. Moreover, a subset of M2 neurons have branching axons that innervate the auditory cortex and the brainstem, providing an anatomical substrate for conveying motor-related signals to the auditory cortex.
Projections from motor cortex to the auditory cortex are an architectural feature common to many mammalian species, including humans and other primates, and are thought to convey information critical for learning and executing complex behaviours, including speech and musicianship. Although movement-related modulation of auditory cortical activity has been detected in monkey and human auditory cortex during a variety of behaviours, a direct role for the motor cortex in these modulatory processes was untested. By applying a wide range of electrophysiological, optical, optogenetic and pharmacological methods in the freely behaving mouse, this study identifies a postsynaptic inhibitory signature of motor action within auditory cortex, a local source of this inhibition, and a long-range motor-to-auditory cortical circuit that engages this local inhibitory mechanism to suppress tone-evoked responses during movement. We found that a wide variety of natural movements strongly suppresses the spontaneous and tone-evoked synaptic activity of auditory cortical excitatory cells and that a substantial fraction of this suppression is mediated through a postsynaptic mechanism involving increased local inhibition via PV+ interneurons. This mechanism contrasts with a disinhibitory mechanism implicated in locomotion-dependent increases in visual cortical responses, with a parallel negative rescaling of excitatory and inhibitory synaptic drive that has been advanced to account for state-dependent changes in auditory cortical responsiveness, and with presynaptic depression driven by state-dependent increases in thalamic activity. Moreover, our observation that this suppression precedes movement onset and persists in masking noise strongly implicates a motor-related signal, rather than sensory reafference or attentional mechanisms. Finally, the finding that movement can suppress ChR2-evoked auditory thalamocortical responses indicates that motor-related suppression of tone-evoked responses is not simply a consequence of peripheral masking by movement-related noise.
The present findings establish that direct ipsilateral projections from M2 to the auditory cortex are sufficient to account for movement-related auditory cortical dynamics and that activity in the ipsilateral M2 is also necessary to sustain these dynamics during movement. However, M2 and the auditory cortex are embedded in complex networks, a consequence of which is that, in addition to directly influencing auditory cortical processing, M2 could also act indirectly through or in concert with neuromodulatory cell groups to modulate auditory cortical dynamics. These findings add to a growing body of evidence that motor-related signals, including those arising from motor cortical regions, can strongly modulate the stimulus-evoked responsiveness of sensory cortical neurons.
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