Reliably detecting unexpected sounds is important for environmental awareness and survival. By selectively reducing responses to frequently, but not rarely, occurring sounds, auditory cortical neurons are thought to enhance the brain's ability to detect unexpected events through stimulus-specific adaptation (SSA). The majority of neurons in the primary auditory cortex exhibit SSA, yet little is known about the underlying cortical circuits. We found that two types of cortical interneurons differentially amplify SSA in putative excitatory neurons. Parvalbumin-positive interneurons (PVs) amplify SSA by providing non-specific inhibition: optogenetic suppression of PVs led to an equal increase in responses to frequent and rare tones. In contrast, somatostatin-positive interneurons (SOMs) selectively reduce excitatory responses to frequent tones: suppression of SOMs led to an increase in responses to frequent, but not to rare tones. A mutually coupled excitatory-inhibitory network model accounts for distinct mechanisms by which cortical inhibitory neurons enhance the brain's sensitivity to unexpected sounds.DOI: http://dx.doi.org/10.7554/eLife.09868.001

Although emotional learning affects sensory acuity, little is known about how these changes are facilitated in the brain. We found that auditory fear conditioning in mice elicited either an increase or a decrease in frequency discrimination acuity depending on how specific the learned response was to the conditioned tone. Using reversible pharmacological inactivation, we found that the auditory cortex mediated learning-evoked changes in acuity in both directions.

The ability to discriminate tones of different frequencies is fundamentally important for everyday hearing. While neurons in the primary auditory cortex (AC) respond differentially to tones of different frequencies, whether and how AC regulates auditory behaviors that rely on frequency discrimination remains poorly understood. Here, we find that the level of activity of inhibitory neurons in AC controls frequency specificity in innate and learned auditory behaviors that rely on frequency discrimination. Photoactivation of parvalbumin-positive interneurons (PVs) improved the ability of the mouse to detect a shift in tone frequency, whereas photosuppression of PVs impaired the performance. Furthermore, photosuppression of PVs during discriminative auditory fear conditioning increased generalization of conditioned response across tone frequencies, whereas PV photoactivation preserved normal specificity of learning. The observed changes in behavioral performance were correlated with bidirectional changes in the magnitude of tone-evoked responses, consistent with predictions of a model of a coupled excitatory-inhibitory cortical network. Direct photoactivation of excitatory neurons, which did not change tone-evoked response magnitude, did not affect behavioral performance in either task. Our results identify a new function for inhibition in the auditory cortex, demonstrating that it can improve or impair acuity of innate and learned auditory behaviors that rely on frequency discrimination.

Understanding how neuronal network activity contributes to memory formation is challenged by the complexity of most brain circuits and the restricted ability to monitor the activity of neuronal populations in vivo. The developing zebrafish (Danio rerio) is an animal model that circumvents these problems, because zebrafish larvae possess a rich behavioral repertoire and an accessible brain. Here, we developed a classical conditioning paradigm in which 6-to 8-d-old larvae develop an enhanced motor response to a visual stimulus (conditioned stimulus, CS) when it is paired with touch (unconditioned stimulus, US). Using in vivo calcium imaging we demonstrate that CS and US activate different subsets of neurons in the cerebellum; their activity, modulated by learning two-photon laser ablation, revealed that the cerebellum is involved in acquisition and extinction, but not the retention, of this memory.

The larval zebrafish is a model organism to study the neural circuitry underlying behavior. There exist, however, few examples of robust long-term memory. Here we describe a simple, unrestrained associative place-conditioning paradigm. We show that visual access to a group of conspecifics has rewarding properties for 6-to 8-day-old larval zebrafish. We use this social reward as an unconditioned stimulus and pair it with a distinct visual environment. After training, larvae exhibited spatial preference for the location previously paired with the social reward for up to 36 h, indicating that zebrafish larvae can exhibit long-term associative memory. Furthermore, incubation with a protein synthesis inhibitor or an NMDAR-antagonist impaired memory. In future experiments, this learning paradigm could be used to study the social interactions of larval zebrafish or paired with cell-specific metabolic labeling to visualize circuits underlying memory formation.