Synaptic Recruitment Enhances Gap Termination Responses in Auditory Cortex.

The ability to detect short gaps in noise is an important tool for assessing the temporal resolution in the auditory cortex. However, the mere existence of responses to temporal gaps bounded by two short broadband markers is surprising, because of the expected short-term suppression that is prevalent in auditory cortex. Here, we used in-vivo intracellular recordings in anesthetized rats to dissect the synaptic mechanisms that underlie gap-related responses. When a gap is bounded by two short markers, a gap termination response was evoked by the onset of the second marker with minimal contribution from the offset of the first marker. Importantly, we show that the gap termination response was driven by a different (potentially partially overlapping) synaptic population than that underlying the onset response to the first marker. This recruitment of additional synaptic resources is a novel mechanism contributing to the important perceptual task of gap detection.

Multiple Timescales Account for Adaptive Responses across Sensory Cortices.

Sensory systems encounter remarkably diverse stimuli in the external environment. Natural stimuli exhibit timescales and amplitudes of variation that span a wide range. Mechanisms of adaptation, a ubiquitous feature of sensory systems, allow for the accommodation of this range of scales. Are there common rules of adaptation across different sensory modalities? We measured the membrane potential responses of individual neurons in the visual, somatosensory, and auditory cortices of male and female mice to discrete, punctate stimuli delivered at a wide range of fixed and nonfixed frequencies. We find that the adaptive profile of the response is largely preserved across these three areas, exhibiting attenuation and responses to the cessation of stimulation, which are signatures of response to changes in stimulus statistics. We demonstrate that these adaptive responses can emerge from a simple model based on the integration of fixed filters operating over multiple time scales.SIGNIFICANCE STATEMENT Our recent sensations affect our current expectations and perceptions of the environment. Neural correlates of this process exist throughout the brain and are loosely termed adaptation. Adaptive processes have been described across sensory cortices, but direct comparisons of these processes have not been possible because paradigms have been tailored specifically for each modality. We developed a common stimulus set that was used to characterize adaptation in somatosensory, visual, and auditory cortex. We describe here the similarities and differences in adaptation across these cortical areas and demonstrate that adaptive responses may emerge from a set of static filters that operate over a broad range of timescales.

Cortical determinants of loudness perception and auditory hypersensitivity.

Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. Here, we observed that activation or inactivation of PVNs functioned like a volume knob in the mouse auditory cortex (ACtx), turning neural and behavioral classification of sound level up or down over a 20dB range. PVN loudness adjustments were "sticky", such that a single bout of 40Hz PVN stimulation sustainably suppressed ACtx sound responsiveness, potentiated feedforward inhibition, and behaviorally desensitized mice to loudness. Sensory sensitivity is a cardinal feature of autism, aging, and peripheral neuropathy, prompting us to ask whether PVN stimulation can persistently desensitize mice with ACtx hyperactivity, PVN hypofunction, and loudness hypersensitivity triggered by cochlear sensorineural damage. We found that a single 16-minute bout of 40Hz PVN stimulation session restored normal loudness perception for one week, showing that perceptual deficits triggered by irreversible peripheral injuries can be reversed through targeted cortical circuit interventions.

Extensive representation of sensory deviance in the responses to auditory gaps in unanesthetized rats.

Unexpected changes in incoming sensory streams are associated with large errors in predicting the deviant stimulus relative to a memory trace of past stimuli. Mismatch negativity (MMN) in human studies and the release from stimulus-specific adaptation (SSA) in animal models correlate with prediction errors and deviance detection.1 In human studies, violation of expectations elicited by an unexpected stimulus omission resulted in an omission MMN.2,3,4,5 These responses are evoked after the expected occurrence time of the omitted stimulus, implying that they reflect the violation of a temporal expectancy.6 Because they are often time locked to the end of the omitted stimulus,4,6,7 they resemble off responses. Indeed, suppression of cortical activity after the termination of the gap disrupts gap detection, suggesting an essential role for offset responses.8 Here, we demonstrate that brief gaps in short noise bursts in the auditory cortex of unanesthetized rats frequently evoke offset responses. Importantly, we show that omission responses are elicited when these gaps are expected but are omitted. These omission responses, together with the release from SSA of both onset and offset responses to rare gaps, form a rich and varied representation of prediction-related signals in the auditory cortex of unanesthetized rats, extending substantially and refining the representations described previously in anesthetized rats.