Information Processing Laboratory, Department of Electronics and Electrical Communication Engineering, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
Advanced Technology Development Centre, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
J Neurosci. 2023 Aug 30;43(35):6141-6163. doi: 10.1523/JNEUROSCI.2353-22.2023. Epub 2023 Aug 4.
Mouse ultrasonic vocalizations (USVs) contain predictable sequential structures like bird songs and speech. Neural representation of USVs in the mouse primary auditory cortex (Au1) and its plasticity with experience has been largely studied with single-syllables or dyads, without using the predictability in USV sequences. Studies using playback of USV sequences have used randomly selected sequences from numerous possibilities. The current study uses mutual information to obtain context-specific natural sequences (NSeqs) of USV syllables capturing the observed predictability in male USVs in different contexts of social interaction with females. Behavioral and physiological significance of NSeqs over random sequences (RSeqs) lacking predictability were examined. Female mice, never having the social experience of being exposed to males, showed higher selectivity for NSeqs behaviorally and at cellular levels probed by expression of immediate early gene c- in Au1. The Au1 supragranular single units also showed higher selectivity to NSeqs over RSeqs. Social-experience-driven plasticity in encoding NSeqs and RSeqs in adult females was probed by examining neural selectivities to the same sequences before and after the above social experience. Single units showed enhanced selectivity for NSeqs over RSeqs after the social experience. Further, using two-photon Ca imaging, we observed social experience-dependent changes in the selectivity of sequences of excitatory and somatostatin-positive inhibitory neurons but not parvalbumin-positive inhibitory neurons of Au1. Using optogenetics, somatostatin-positive neurons were identified as a possible mediator of the observed social-experience-driven plasticity. Our study uncovers the importance of predictive sequences and introduces mouse USVs as a promising model to study context-dependent speech like communications. Humans need to detect patterns in the sensory world. For instance, speech is meaningful sequences of acoustic tokens easily differentiated from random ordered tokens. The structure derives from the predictability of the tokens. Similarly, mouse vocalization sequences have predictability and undergo context-dependent modulation. Our work investigated whether mice differentiate such informative predictable sequences (NSeqs) of communicative significance from RSeqs at the behavioral, molecular, and neuronal levels. Following a social experience in which NSeqs occur as a crucial component, mouse auditory cortical neurons become more sensitive to differences between NSeqs and RSeqs, although preference for individual tokens is unchanged. Thus, speech-like communication and its dysfunction may be studied in circuit, cellular, and molecular levels in mice.
小鼠超声发声（USVs）包含可预测的序列结构，如鸟鸣和言语。在小鼠初级听觉皮层（Au1）中，USVs 的神经表示及其随经验的可塑性已在很大程度上通过单音节或双音节进行研究，而没有利用 USV 序列中的可预测性。使用 USV 序列回放的研究使用了从众多可能性中随机选择的序列。本研究使用互信息获得特定于上下文的自然 USV 音节序列（NSeqs），这些序列捕捉了雄性 USV 在与雌性社交互动的不同背景下观察到的可预测性。通过在 Au1 中探测即时早期基因 c-的表达，研究了 NSeqs 相对于缺乏可预测性的随机序列（RSeqs）在行为和生理上的意义。从未有过接触雄性社交经验的雌性小鼠在行为和 Au1 的细胞水平上对 NSeqs 表现出更高的选择性。Au1 超颗粒的单个单元对 NSeqs 相对于 RSeqs 的选择性也更高。通过检查在上述社交经验前后对相同序列的神经选择性，研究了成年雌性中编码 NSeqs 和 RSeqs 的社交经验驱动的可塑性。在社交经验之后，单个单元对 NSeqs 相对于 RSeqs 的选择性增强。此外，使用双光子 Ca 成像，我们观察到 Au1 兴奋性和生长抑素阳性抑制神经元序列的选择性，但不观察到钙结合蛋白阳性抑制神经元序列的选择性发生社交经验依赖性变化。使用光遗传学，鉴定出生长抑素阳性神经元可能是观察到的社交经验驱动可塑性的介导者。我们的研究揭示了预测序列的重要性，并引入了小鼠 USVs 作为研究类似上下文的言语交流的有前途的模型。人类需要在感官世界中发现模式。例如，言语是可区分的声学令牌的有意义序列，与随机有序令牌不同。结构源于令牌的可预测性。同样，小鼠发声序列具有可预测性，并受到上下文的调制。我们的工作研究了小鼠是否在行为、分子和神经元水平上从 RSeqs 中区分出具有这种信息预测性的通讯意义的序列（NSeqs）。在发生 NSeqs 作为关键组成部分的社交体验之后，尽管对单个令牌的偏好保持不变，但小鼠听觉皮层神经元对 NSeqs 和 RSeqs 之间的差异变得更加敏感。因此，可以在小鼠的电路、细胞和分子水平上研究类似言语的交流及其功能障碍。
