A distributed auditory network mediated by pontine central gray underlies ultra-fast awakening in response to alerting sounds.

Sleeping animals can be woken up rapidly by external threat signals, which is an essential defense mechanism for survival. However, neuronal circuits underlying the fast transmission of sensory signals for this process remain unclear. Here, we report in mice that alerting sound can induce rapid awakening within hundreds of milliseconds and that glutamatergic neurons in the pontine central gray (PCG) play an important role in this process. These neurons exhibit higher sensitivity to auditory stimuli in sleep than wakefulness. Suppressing these neurons results in reduced sound-induced awakening and increased sleep in intrinsic sleep/wake cycles, whereas their activation induces ultra-fast awakening from sleep and accelerates awakening from anesthesia. Additionally, the sound-induced awakening can be attributed to the propagation of auditory signals from the PCG to multiple arousal-related regions, including the mediodorsal thalamus, lateral hypothalamus, and ventral tegmental area. Thus, the PCG serves as an essential distribution center to orchestrate a global auditory network to promote rapid awakening.

Glutamatergic and GABAergic neurons in pontine central gray mediate opposing valence-specific behaviors through a global network.

Extracting the valence of environmental cues is critical for animals' survival. How valence in sensory signals is encoded and transformed to produce distinct behavioral responses remains not well understood. Here, we report that the mouse pontine central gray (PCG) contributes to encoding both negative and positive valences. PCG glutamatergic neurons were activated selectively by aversive, but not reward, stimuli, whereas its GABAergic neurons were preferentially activated by reward signals. The optogenetic activation of these two populations resulted in avoidance and preference behavior, respectively, and was sufficient to induce conditioned place aversion/preference. Suppression of them reduced sensory-induced aversive and appetitive behaviors, respectively. These two functionally opponent populations, receiving a broad range of inputs from overlapping yet distinct sources, broadcast valence-specific information to a distributed brain network with distinguishable downstream effectors. Thus, PCG serves as a critical hub to process positive and negative valences of incoming sensory signals and drive valence-specific behaviors with distinct circuits.

Selectivity of Monaural Synaptic Inputs Underlying Binaural Auditory Information Integration in the Central Nucleus of Inferior Colliculus.

Neurons in the central nucleus of the inferior colliculus (ICC) receive ascending inputs from the ipsilateral and contralateral auditory pathway. However, the contributions of excitatory or inhibitory synaptic inputs evoked by ipsilateral and contralateral stimuli to auditory responses of ICC neurons remain unclear. Using in vivo whole-cell voltage-clamp recordings, we investigated excitatory and inhibitory synaptic currents in neurons of the ICC in response to binaural stimulation by performing an intensity-intensity scan. To systematically analyze the contribution of the ipsilateral and contralateral ear, the sound intensity was randomly delivered to each side from 0 dB sound pressure level (SPL) to 70 dB SPL. Although the synaptic responses were dominated by contralateral inputs at weak sound intensities, they could be increased (or decreased) by additional ipsilateral stimulation at higher intensities. Interestingly, the synaptic responses to contralateral acoustic inputs were not linearly superimposed with the ipsilateral ones. By contrast, the responses showed either a contralateral or ipsilateral profile, depending on which one was more dominant. This change occurred at a certain intensity "switch" point. Thus, the binaural auditory responses of the ICC neurons were not simply mediated by the summation of the inputs evoked by ipsilateral and contralateral stimulations. This suggested that the ICC might inherit the acoustic information integrated at the brainstem, causing the selectivity of monaural excitation and inhibition to underlie the neuronal binaural acoustic response.

Septal and Hippocampal Neurons Contribute to Auditory Relay and Fear Conditioning.

The hippocampus has been thought to process auditory information. However, the properties, pathway, and role of hippocampal auditory responses are unclear. With loose-patch recordings, we found that hippocampal neurons are mainly responsive to noise and are not tonotopically organized. Their latencies are shorter than those of primary auditory cortical (A1) neurons but longer than those of medial septal (MS) neurons, suggesting that hippocampal auditory information comes from MS neurons rather than from A1 neurons. Silencing the MS blocks both hippocampal auditory responses and memory of auditory fear conditioning trained with noise and tone. Auditory fear conditioning was associated with some cues but not with a specific frequency of sound, as demonstrated by animals trained with noise, 2.5-, 5-, 10-, 15-, or 30-kHz tones, and tested with these sounds. Therefore, the noise responses of hippocampal neurons have identified a population of neurons that can be associated with auditory fear conditioning.