<p>Data for Fig 1.</p>

Inhibition plays an important role in controlling the flow and processing of auditory information throughout the central auditory pathway, yet how inhibitory circuits shape auditory processing in the medial geniculate body (MGB), the key region in the auditory thalamus, is poorly understood. The MGB gates the flow of auditory information to the auditory cortex, and it is inhibited largely by the thalamic reticular nucleus (TRN). The TRN contains two major classes of inhibitory neurons: parvalbumin (PVTRN)-positive and somatostatin (SSTTRN)-positive neurons. PV and SST neurons have been shown to play differential roles in controlling sound responses in auditory cortex. In the somatosensory and visual subregions of the TRN, PVTRN and SSTTRN neurons exhibit anatomical and functional differences. However, it remains unknown whether and how PVTRN and SSTTRN neurons differ in their anatomical projections from the TRN to the auditory thalamus, and whether and how they differentially modulate activity in the MGB. Here, we investigated virally labeled projections of PVTRN or SSTTRN neurons, and recorded neuronal responses in the MGB of awake, head-fixed mice while presenting sound stimuli and selectivity suppressing PVTRN or SSTTRN neurons on a subset of trials. We find that PVTRN and SSTTRN neurons exhibit differential projection patterns within the auditory thalamus: PVTRN neurons predominantly project to ventral MGB, whereas SSTTRN neurons project to the dorso-medial regions of MGB. Optogenetic inactivation of PVTRN neurons bidirectionally modulated sound-evoked activity in MGB, increasing firing in 29% of MGB neurons, while suppressing firing in 41%. In contrast, inactivating SSTTRN neurons largely suppressed tone-evoked activity in MGB neurons. Cell type-specific computational models identified candidate circuit mechanisms for generating the differential effects of TRN inactivation on MGB sound responses. These distinct inhibitory pathways within the auditory thalamus reveal cell type-specific organization of thalamic inhibition in auditory computation.

抑制作用在整条听觉中枢通路中，对听觉信息的传递与加工调控发挥着核心作用，然而作为听觉丘脑（auditory thalamus）关键区域的内侧膝状体（medial geniculate body, MGB）内的抑制环路如何塑造听觉加工过程，目前仍不甚明晰。内侧膝状体是听觉信息向听觉皮层（auditory cortex）传递的门户，其活动主要受丘脑网状核（thalamic reticular nucleus, TRN）的抑制性调控。丘脑网状核包含两大类抑制性神经元：小白蛋白阳性（PVTRN，parvalbumin-positive）神经元与生长抑素阳性（SSTTRN，somatostatin-positive）神经元。已有研究证实，小白蛋白与生长抑素神经元在调控听觉皮层的声音响应中发挥着截然不同的作用。在丘脑网状核的躯体感觉与视觉亚区内，PVTRN与SSTTRN神经元已被发现存在解剖结构与功能上的差异。然而，目前仍不清楚PVTRN与SSTTRN神经元从丘脑网状核到听觉丘脑的解剖投射模式是否存在差异，以及二者如何差异性调控内侧膝状体的神经元活动。本研究通过病毒标记示踪PVTRN与SSTTRN神经元的投射，并在清醒头部固定小鼠的内侧膝状体内记录神经元响应；实验中同步呈现声音刺激，并在部分试次中选择性抑制PVTRN或SSTTRN神经元的活动。研究结果显示，PVTRN与SSTTRN神经元在听觉丘脑内的投射模式存在显著差异：PVTRN神经元主要投射至腹侧内侧膝状体，而SSTTRN神经元则投射至内侧膝状体的背内侧区域。对PVTRN神经元进行光遗传抑制（optogenetic inactivation）后，可双向调控内侧膝状体的声音诱发性活动：29%的内侧膝状体神经元放电频率升高，而41%的神经元放电受到抑制。与之形成鲜明对比的是，抑制SSTTRN神经元的活动后，内侧膝状体神经元的音调诱发性活动整体受到显著抑制。基于细胞类型特异性（cell type-specific）的计算模型，本研究进一步明确了丘脑网状核抑制对内侧膝状体声音响应产生差异化影响的潜在环路机制。听觉丘脑内的这些差异化抑制通路，揭示了听觉计算过程中丘脑抑制作用的细胞类型特异性组织模式。