More than the end: OFF response plasticity as a mnemonic signature of a sound's behavioral salience.

In studying how neural populations in sensory cortex code dynamically varying stimuli to guide behavior, the role of spiking after stimuli have ended has been underappreciated. This is despite growing evidence that such activity can be tuned, experience-and context-dependent and necessary for sensory decisions that play out on a slower timescale. Here we review recent studies, focusing on the auditory modality, demonstrating that this so-called OFF activity can have a more complex temporal structure than the purely phasic firing that has often been interpreted as just marking the end of stimuli. While diverse and still incompletely understood mechanisms are likely involved in generating phasic and tonic OFF firing, more studies point to the continuing post-stimulus activity serving a short-term, stimulus-specific mnemonic function that is enhanced when the stimuli are particularly salient. We summarize these results with a conceptual model highlighting how more neurons within the auditory cortical population fire for longer duration after a sound's termination during an active behavior and can continue to do so even while passively listening to behaviorally salient stimuli. Overall, these studies increasingly suggest that tonic auditory cortical OFF activity holds an echoic memory of specific, salient sounds to guide behavioral decisions.

Parent TRAP: Discriminating Infant Cries Requires a Higher-Order Auditory Association Area in Mice.

A circuit understanding of how perception links to response requires integrating neural connectivity, activity, and behavior. In this issue of Neuron, Tasaka et al. (2020) target neurons activated by ultrasonic pup vocalizations and discover a functional synaptic network embedded through acoustically selective TeA neurons that help link the calls to a discriminative maternal behavioral response.

Experience-Dependent Coding of Time-Dependent Frequency Trajectories by Off Responses in Secondary Auditory Cortex.

Time-dependent frequency trajectories are an inherent feature of many behaviorally relevant sounds, such as species-specific vocalizations. Dynamic frequency trajectories, even in short sounds, often convey meaningful information, which may be used to differentiate sound categories. However, it is not clear what and where neural responses in the auditory cortical pathway are critical for conveying information about behaviorally relevant frequency trajectories, and how these responses change with experience. Here, we uncover tuning to subtle variations in frequency trajectories in auditory cortex of female mice. We found that auditory cortical responses could be modulated by variations in a pure tone trajectory as small as 1/24th of an octave, comparable to what has been reported in primates. In particular, late spiking after the end of a sound stimulus was more often sensitive to the sound's subtle frequency variation compared with spiking during the sound. Such "Off" responses in the adult A2, but not those in core auditory cortex, were plastic in a way that may enhance the representation of a newly acquired, behaviorally relevant sound category. We illustrate this with the maternal mouse paradigm for natural vocalization learning. By using an ethologically inspired paradigm to drive auditory responses in higher-order neurons, our results demonstrate that mouse auditory cortex can track fine frequency changes, which allows A2 Off responses in particular to better respond to pitch trajectories that distinguish behaviorally relevant, natural sound categories.SIGNIFICANCE STATEMENT A whistle's pitch conveys meaning to its listener, as when dogs learn that distinct pitch trajectories whistled by their owner differentiate specific commands. Many species use pitch trajectories in their own vocalizations to distinguish sound categories, such as in human languages, such as Mandarin. How and where auditory neural activity encodes these pitch trajectories as their meaning is learned but not well understood, especially for short-duration sounds. We studied this in mice, where infants use ultrasonic whistles to communicate to adults. We found that late neural firing after a sound ends can be tuned to how the pitch changes in time, and that this response in a secondary auditory cortical field changes with experience to acquire a pitch change's meaning.