The role of cortical interneurons in auditory processing and learning

描述(申请人提供)：听觉感知依赖于我们区分不同声音的频谱内容的能力，并学习使用这种差异来区分与行为相关的(如危险和安全的)声音。初级听觉皮质(A1)在频率辨别和听觉辨别性情绪学习中起着重要的调节作用。然而，尽管几十年的研究已经仔细绘制了A1中神经元的听觉反应特性，但这种调制背后的神经元电路目前尚不清楚。该提案的目的是测试这种候选神经元回路的作用。在这个方案中，我们检验了一种假设，即最常见的一类中间神经元--小白蛋白阳性神经元(PV)的活动调节了A1区兴奋性神经元对不同频率的音调的选择性，并且PV的活动影响了频率辨别和辨别性听觉情绪学习的行为表现。为了测量PV活动的影响，我们使用最近开发的光遗传系统，在清醒行为的小鼠中选择性地、时间上精确地激活或抑制PV中间神经元，并将PV激活或失活期间的神经计量学和行为表现与基线条件进行比较。

DESCRIPTION (provided by applicant): Hearing perception relies on our ability to tell apart the spectral content of different sounds, and to learn to use this difference to distinguish behaviorally relevant (such as dangerous and safe) sounds. The primary auditory cortex (A1) has been shown to play an important modulatory role in frequency discrimination and auditory discriminative emotional learning. However, despite decades of research that have carefully mapped the auditory response properties of neurons in A1, the neuronal circuits that underlie this modulation are currently unknown. The goal of the proposal is to test the role of such candidate neuronal circuit. In this proposal, we test the hypothesis that the activity of the most common class of interneurons, parvalbumin- positive (PVs), modulates selectivity to tones at different frequencies of excitatory neurons in A1, and that PV activity affects the behavioral performance in frequency discrimination and precision of discriminative auditory emotional learning. To measure the effect of PV activity we activate or inhibit PV interneurons selectively and temporally precisely using a recently developed optogenetic system, in awake behaving mice, and compare the neurometric and behavioral performance during activation or inactivation of PVs to baseline condition.