Subcortical circuits mediate communication between primary sensory cortical areas in mice.

Integration of information across the senses is critical for perception and is a common property of neurons in the cerebral cortex, where it is thought to arise primarily from corticocortical connections. Much less is known about the role of subcortical circuits in shaping the multisensory properties of cortical neurons. We show that stimulation of the whiskers causes widespread suppression of sound-evoked activity in mouse primary auditory cortex (A1). This suppression depends on the primary somatosensory cortex (S1), and is implemented through a descending circuit that links S1, via the auditory midbrain, with thalamic neurons that project to A1. Furthermore, a direct pathway from S1 has a facilitatory effect on auditory responses in higher-order thalamic nuclei that project to other brain areas. Crossmodal corticofugal projections to the auditory midbrain and thalamus therefore play a pivotal role in integrating multisensory signals and in enabling communication between different sensory cortical areas.

Neural circuits underlying auditory contrast gain control and their perceptual implications.

Neural adaptation enables sensory information to be represented optimally in the brain despite large fluctuations over time in the statistics of the environment. Auditory contrast gain control represents an important example, which is thought to arise primarily from cortical processing. Here we show that neurons in the auditory thalamus and midbrain of mice show robust contrast gain control, and that this is implemented independently of cortical activity. Although neurons at each level exhibit contrast gain control to similar degrees, adaptation time constants become longer at later stages of the processing hierarchy, resulting in progressively more stable representations. We also show that auditory discrimination thresholds in human listeners compensate for changes in contrast, and that the strength of this perceptual adaptation can be predicted from physiological measurements. Contrast adaptation is therefore a robust property of both the subcortical and cortical auditory system and accounts for the short-term adaptability of perceptual judgments.

Development, organization and plasticity of auditory circuits: Lessons from a cherished colleague.

Ray Guillery was a neuroscientist known primarily for his ground-breaking studies on the development of the visual pathways and subsequently on the nature of thalamocortical processing loops. The legacy of his work, however, extends well beyond the visual system. Thanks to Ray Guillery's pioneering anatomical studies, the ferret has become a widely used animal model for investigating the development and plasticity of sensory processing. This includes our own work on the auditory system, where experiments in ferrets have revealed the role of sensory experience during development in shaping the neural circuits responsible for sound localization, as well as the capacity of the mature brain to adapt to changes in inputs resulting from hearing loss. Our research has also built on Ray Guillery's ideas about the possible functions of the massive descending projections that link sensory areas of the cerebral cortex to the thalamus and other subcortical targets, by demonstrating a role for corticothalamic feedback in the perception of complex sounds and for corticollicular projection neurons in learning to accommodate altered auditory spatial cues. Finally, his insights into the organization and functions of transthalamic corticocortical connections have inspired a raft of research, including by our own laboratory, which has attempted to identify how information flows through the thalamus.

A Role for Auditory Corticothalamic Feedback in the Perception of Complex Sounds.

Feedback signals from the primary auditory cortex (A1) can shape the receptive field properties of neurons in the ventral division of the medial geniculate body (MGBv). However, the behavioral significance of corticothalamic modulation is unknown. The aim of this study was to elucidate the role of this descending pathway in the perception of complex sounds. We tested the ability of adult female ferrets to detect the presence of a mistuned harmonic in a complex tone using a positive conditioned go/no-go behavioral paradigm before and after the input from layer VI in A1 to MGBv was bilaterally and selectively eliminated using chromophore-targeted laser photolysis. MGBv neurons were identified by their short latencies and sharp tuning curves. They responded robustly to harmonic complex tones and exhibited an increase in firing rate and temporal pattern changes when one frequency component in the complex tone was mistuned. Injections of fluorescent microbeads conjugated with a light-sensitive chromophore were made in MGBv, and, following retrograde transport to the cortical cell bodies, apoptosis was induced by infrared laser illumination of A1. This resulted in a selective loss of ∼60% of layer VI A1-MGBv neurons. After the lesion, mistuning detection was impaired, as indicated by decreased d' values, a shift of the psychometric curves toward higher mistuning values, and increased thresholds, whereas discrimination performance was unaffected when level cues were also available. Our results suggest that A1-MGBv corticothalamic feedback contributes to the detection of harmonicity, one of the most important grouping cues in the perception of complex sounds.SIGNIFICANCE STATEMENT Perception of a complex auditory scene is based on the ability of the brain to group those sound components that belong to the same source and to segregate them from those belonging to different sources. Because two people talking simultaneously may differ in their voice pitch, perceiving the harmonic structure of sounds is very important for auditory scene analysis. Here we demonstrate mistuning sensitivity in the thalamus and that feedback from the primary auditory cortex is required for the normal ability of ferrets to detect a mistuned harmonic within a complex sound. These results provide novel insight into the function of descending sensory pathways in the brain and suggest that this corticothalamic circuit plays an important role in scene analysis.

Mistuning detection performance of ferrets in a go/no-go task.

The harmonic structure of sounds is an important grouping cue in auditory scene analysis. The ability of ferrets to detect mistuned harmonics was measured using a go/no-go task paradigm. Psychometric functions plotting sensitivity as a function of degree of mistuning were used to evaluate behavioral performance using signal detection theory. The mean (± standard error of the mean) threshold for mistuning detection was 0.8 ± 0.1 Hz, with sensitivity indices and reaction times depending on the degree of mistuning. These data provide a basis for investigation of the neural basis for the perception of complex sounds in ferrets, an increasingly used animal model in auditory research.

Lesions of the auditory cortex impair azimuthal sound localization and its recalibration in ferrets.

The role of auditory cortex in sound localization and its recalibration by experience was explored by measuring the accuracy with which ferrets turned toward and approached the source of broadband sounds in the horizontal plane. In one group, large bilateral lesions were made of the middle ectosylvian gyrus, where the primary auditory cortical fields are located, and part of the anterior and/or posterior ectosylvian gyrus, which contain higher-level fields. In the second group, the lesions were intended to be confined to primary auditory cortex (A1). The ability of the animals to localize noise bursts of different duration and level was measured before and after the lesions were made. A1 lesions produced a modest disruption of approach-to-target responses to short-duration stimuli (<500 ms) on both sides of space, whereas head orienting accuracy was unaffected. More extensive lesions produced much greater auditory localization deficits, again primarily for shorter sounds. In these ferrets, the accuracy of both the approach-to-target behavior and the orienting responses was impaired, and they could do little more than correctly lateralize the stimuli. Although both groups of ferrets were still able to localize long-duration sounds accurately, they were, in contrast to ferrets with an intact auditory cortex, unable to relearn to localize these stimuli after altering the spatial cues available by reversibly plugging one ear. These results indicate that both primary and nonprimary cortical areas are necessary for normal sound localization, although only higher auditory areas seem to contribute to accurate head orienting behavior. They also show that the auditory cortex, and A1 in particular, plays an essential role in training-induced plasticity in adult ferrets, and that this is the case for both head orienting responses and approach-to-target behavior.

Physiological and anatomical evidence for multisensory interactions in auditory cortex.

Recent studies, conducted almost exclusively in primates, have shown that several cortical areas usually associated with modality-specific sensory processing are subject to influences from other senses. Here we demonstrate using single-unit recordings and estimates of mutual information that visual stimuli can influence the activity of units in the auditory cortex of anesthetized ferrets. In many cases, these units were also acoustically responsive and frequently transmitted more information in their spike discharge patterns in response to paired visual-auditory stimulation than when either modality was presented by itself. For each stimulus, this information was conveyed by a combination of spike count and spike timing. Even in primary auditory areas (primary auditory cortex [A1] and anterior auditory field [AAF]), approximately 15% of recorded units were found to have nonauditory input. This proportion increased in the higher level fields that lie ventral to A1/AAF and was highest in the anterior ventral field, where nearly 50% of the units were found to be responsive to visual stimuli only and a further quarter to both visual and auditory stimuli. Within each field, the pure-tone response properties of neurons sensitive to visual stimuli did not differ in any systematic way from those of visually unresponsive neurons. Neural tracer injections revealed direct inputs from visual cortex into auditory cortex, indicating a potential source of origin for the visual responses. Primary visual cortex projects sparsely to A1, whereas higher visual areas innervate auditory areas in a field-specific manner. These data indicate that multisensory convergence and integration are features common to all auditory cortical areas but are especially prevalent in higher areas.