Recent research in mice indicates that luminance-independent fluctuations in pupil size predict variability in spontaneous and evoked activity of single neurons in auditory and visual cortex. These findings suggest that pupil is an indicator of large-scale changes in arousal state that affect sensory processing. However, it is not known whether pupil-related state also influences the selectivity of auditory neurons. We recorded pupil size and single-unit spiking activity in the primary auditory cortex (A1) of nonanesthetized male and female ferrets during presentation of natural vocalizations and tone stimuli that allow measurement of frequency and level tuning. Neurons showed a systematic increase in both spontaneous and sound-evoked activity when pupil was large, as well as desynchronization and a decrease in trial-to-trial variability. Relationships between pupil size and firing rate were nonmonotonic in some cells. In most neurons, several measurements of tuning, including acoustic threshold, spectral bandwidth, and best frequency, remained stable across large changes in pupil size. Across the population, however, there was a small but significant decrease in acoustic threshold when pupil was dilated. In some recordings, we observed rapid, saccade-like eye movements during sustained pupil constriction, which may indicate sleep. Including the presence of this state as a separate variable in a regression model of neural variability accounted for some, but not all, of the variability and nonmonotonicity associated with changes in pupil size. NEW & NOTEWORTHY Cortical neurons vary in their response to repeated stimuli, and some portion of the variability is due to fluctuations in network state. By simultaneously recording pupil and single-neuron activity in auditory cortex of ferrets, we provide new evidence that network state affects the excitability of auditory neurons, but not sensory selectivity. In addition, we report the occurrence of possible sleep states, adding to evidence that pupil provides an index of both sleep and physiological arousal.

Auditory selective attention is required for parsing crowded acoustic environments, but cortical systems mediating the influence of behavioral state on auditory perception are not well characterized. Previous neurophysiological studies suggest that attention produces a general enhancement of neural responses to important target sounds versus irrelevant distractors. However, behavioral studies suggest that in the presence of masking noise, attention provides a focal suppression of distractors that compete with targets. Here, we compared effects of attention on cortical responses to masking versus non-masking distractors, controlling for effects of listening effort and general task engagement. We recorded single-unit activity from primary auditory cortex (A1) of ferrets during behavior and found that selective attention decreased responses to distractors masking targets in the same spectral band, compared with spectrally distinct distractors. This suppression enhanced neural target detection thresholds, suggesting that limited attention resources serve to focally suppress responses to distractors that interfere with target detection. Changing effort by manipulating target salience consistently modulated spontaneous but not evoked activity. Task engagement and changing effort tended to affect the same neurons, while attention affected an independent population, suggesting that distinct feedback circuits mediate effects of attention and effort in A1.

Both generalized arousal and engagement in a specific task influence sensory neural processing. To isolate effects of these state variables in the auditory system, we recorded single-unit activity from primary auditory cortex (A1) and inferior colliculus (IC) of ferrets during a tone detection task, while monitoring arousal via changes in pupil size. We used a generalized linear model to assess the influence of task engagement and pupil size on sound-evoked activity. In both areas, these two variables affected independent neural populations. Pupil size effects were more prominent in IC, while pupil and task engagement effects were equally likely in A1. Task engagement was correlated with larger pupil; thus, some apparent effects of task engagement should in fact be attributed to fluctuations in pupil size. These results indicate a hierarchy of auditory processing, where generalized arousal enhances activity in midbrain, and effects specific to task engagement become more prominent in cortex.

Perception of vocalizations and other behaviorally relevant sounds requires integrating acoustic information over hundreds of milliseconds. Sound-evoked activity in auditory cortex typically has much shorter latency, but the acoustic context, i.e., sound history, can modulate sound evoked activity over longer periods. Contextual effects are attributed to modulatory phenomena, such as stimulus-specific adaption and contrast gain control. However, an encoding model that links context to natural sound processing has yet to be established. We tested whether a model in which spectrally tuned inputs undergo adaptation mimicking short-term synaptic plasticity (STP) can account for contextual effects during natural sound processing. Single-unit activity was recorded from primary auditory cortex of awake ferrets during presentation of noise with natural temporal dynamics and fully natural sounds. Encoding properties were characterized by a standard linear-nonlinear spectro-temporal receptive field (LN) model and variants that incorporated STP-like adaptation. In the adapting models, STP was applied either globally across all input spectral channels or locally to subsets of channels. For most neurons, models incorporating local STP predicted neural activity as well or better than LN and global STP models. The strength of nonlinear adaptation varied across neurons. Within neurons, adaptation was generally stronger for spectral channels with excitatory than inhibitory gain. Neurons showing improved STP model performance also tended to undergo stimulus-specific adaptation, suggesting a common mechanism for these phenomena. When STP models were compared between passive and active behavior conditions, response gain often changed, but average STP parameters were stable. Thus, spectrally and temporally heterogeneous adaptation, subserved by a mechanism with STP-like dynamics, may support representation of the complex spectro-temporal patterns that comprise natural sounds across wide-ranging sensory contexts.

Recent research indicates that luminance-independent fluctuations in pupil size predict variability in spontaneous and evoked activity of single neurons in auditory and visual cortex. These findings suggest that pupil is an indicator of large-scale changes in arousal state that affect sensory processing. It is not known whether pupil-related state also influences the selectivity of auditory neurons. We recorded pupil size and single-unit spiking activity in the primary auditory cortex (A1) of ferrets during presentation of vocalizations and tone stimuli. Neurons showed a systematic increase in both spontaneous and sound-evoked activity when pupil was large, as well as a decrease in trial-to-trial variability. Relationships between pupil size and firing rate were non-monotonic in some cells. In most neurons, several measurements of tuning, including acoustic threshold, spectral bandwidth, and best frequency, remained stable across large changes in pupil size. Across the population, however, there was a small but significant decrease in acoustic threshold when pupil was dilated. In some recordings, we observed rapid, saccade-like eye movements during sustained pupil constriction, which may indicate episodes of rapid eye movement sleep. Including the presence of this state as a separate variable in a regression model of neural variability accounted for some, but not all, of the variability associated with changes in pupil size.