Suri Harini, Salgado-Puga Karla, Wang Yixuan, Allen Nayomie, Lane Kaitlynn, Granroth Kyra, Olivei Alberto, Nass Nathanial, Rothschild Gideon
Department of Psychology, University of Michigan, Ann Arbor, Michigan, United States of America.
Kresge Hearing Research Institute and Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS Biol. 2025 Jun 2;23(6):e3003209. doi: 10.1371/journal.pbio.3003209. eCollection 2025 Jun.
A crucial aspect of auditory perception is the ability to use sound cues to predict future events and to time actions accordingly. For example, the sound of an approaching vehicle signals when it is safe to cross the street; distinct smartphone notification sounds reflect a call that needs to be answered within a few seconds, or a text that can be read later. Other animals similarly use sounds to plan, time and execute behaviors such as hunting, evading predation and tending to offspring. However, the neural mechanisms that underlie sound-guided prediction of upcoming salient event timing are not well understood. To address this gap, we employed an appetitive sound-triggered reward time prediction behavior in head-fixed mice. We find that mice trained on this task reliably estimate the time from a sound cue to upcoming reward on the scale of a few seconds, as demonstrated by learning-dependent well-timed increases in predictive licking for reward. Moreover, mice showed a dramatic impairment in their ability to use sound to predict delayed reward when the auditory cortex was inactivated, demonstrating its causal involvement. To identify the neurophysiological signatures of auditory cortical reward-timing prediction, we recorded local field potentials during learning and performance of this behavior and found that the magnitude of auditory cortical responses to the sound prospectively encoded the duration of the anticipated sound-reward time interval. Next, we explored how and where these sound-triggered time interval prediction signals propagate from the auditory cortex to time and initiate consequent action. We targeted the monosynaptic projections from the auditory cortex to the posterior striatum and found that chemogenetic inactivation of these projections impaired animals' ability to predict sound-triggered delayed reward. Simultaneous neural recordings in the auditory cortex and posterior striatum during task performance revealed coordination of neural activity across these regions during the sound cue predicting the time interval to reward. Collectively, our findings identify an auditory cortical-striatal circuit supporting sound-triggered timing-prediction behaviors.
听觉感知的一个关键方面是利用声音线索预测未来事件并据此安排行动时间的能力。例如，一辆正在靠近的车辆发出的声音能提示何时过马路是安全的；智能手机不同的通知声音则反映出是需要在几秒钟内接听的电话，还是稍后可以查看的短信。其他动物同样会利用声音来计划、安排和执行诸如捕猎、躲避捕食以及照料后代等行为。然而，声音引导下对即将发生的显著事件时间进行预测的神经机制尚未得到充分理解。为了填补这一空白，我们在头部固定的小鼠中采用了一种基于声音触发奖励的时间预测行为。我们发现，经过此项任务训练的小鼠能够可靠地估计从声音线索到即将到来的奖励之间的时间，时间范围在几秒内，这通过对奖励的预测性舔舐行为中与学习相关的适时增加得以证明。此外，当听觉皮层被失活时，小鼠利用声音预测延迟奖励的能力出现了显著损伤，这表明听觉皮层在其中起到了因果作用。为了确定听觉皮层奖励时间预测的神经生理学特征，我们在这种行为的学习和执行过程中记录了局部场电位，发现听觉皮层对声音的反应幅度前瞻性地编码了预期的声音 - 奖励时间间隔的持续时间。接下来，我们探究了这些声音触发的时间间隔预测信号如何以及从何处从听觉皮层传播出去，以安排并启动后续行动。我们针对从听觉皮层到后纹状体的单突触投射进行研究，发现对这些投射进行化学遗传学失活会损害动物预测声音触发的延迟奖励的能力。在任务执行过程中对听觉皮层和后纹状体进行同步神经记录发现，在声音线索预测奖励时间间隔期间，这些区域的神经活动存在协同作用。总体而言，我们的研究结果确定了一个支持声音触发的时间预测行为的听觉皮层 - 纹状体回路。
