Influence of T-Stellate Cell Input on Sound Processing in the Inferior Colliculus

T 星状细胞输入对下丘声音处理的影响

• 批准号: 10824666
• 负责人: Yoani Natalie Herrera
• 金额: $ 4.08万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10824666
• 关键词: Acoustic Nerve; Address; Agonist; Auditory; Auditory system; Brain; Brain Stem; Cell Nucleus; Cells; Cochlear Implants; Cochlear nucleus; Code; Communication; Cueing for speech; Cues; Data; Dementia; Dendrites; Electrophysiology (science); Equilibrium; Evoked Potentials; Excitatory Postsynaptic Potentials; Exhibits; Fluorescence; Frequencies; Genetic; Glutamates; Goals; Health; Hearing Aids; Human; Impaired cognition; In Vitro; Individual; Inferior Colliculus; Intervention; Kinetics; Knowledge; Label; Light; Link; Maps; Mental Depression; Midbrain structure; Neurons; Opsin; Pathway interactions; Pharmacology; Play; Population; Prevalence; Process; Research; Role; Shapes; Signal Transduction; Silicon; Slice; Social isolation; Source; Speech; Stimulus; Synapses; System; Testing; Vasoactive Intestinal Peptide; Whole-Cell Recordings; auditory pathway; auditory processing; cell type; excitatory neuron; experimental study; genetic approach; hearing impairment; in vivo; inhibitory neuron; insight; molecular marker; neural circuit; neuronal excitability; neuropeptide Y; novel; optogenetics; patch clamp; pharmacologic; receptor; recruit; response; signal processing; sound; sound frequency; speech processing; stellate cell; synaptic depression; vocalization

Abstract: The inferior colliculus (IC) is the midbrain hub of the auditory system and is important for the processing of speech and other vocalizations. T-stellate neurons provide the only direct projection from the anteroventral cochlear nucleus (AVCN) to the IC and have been implicated in the processing of vocalization cues since they encode information about sound frequency and amplitude modulations (AM). However, how T- stellate cells influence specific populations of IC neurons and how they shape speech and vocalization coding in the IC is unknown. One barrier to studying T-stellate input to the IC has been a lack of molecular markers for IC neuron classes. Recently, we overcame this barrier by identifying two novel classes of IC neurons: glutamatergic VIP neurons and GABAergic NPY neurons. Together, VIP and NPY neurons represent ~55-75% of stellate cells within the central nucleus of the IC. Using channelrhodopsin assisted circuit mapping and fluorescence-targeted whole cell recordings in brain slices, our preliminary data show that both VIP and NPY neurons receive functional synaptic input from T-stellate cells. Interestingly, the excitatory postsynaptic potentials (EPSPs) evoked by T-stellate input to NPY neurons are larger in amplitude than those evoked in VIP neurons. In addition, optogenetic activation of T-stellate terminals can elicit feedforward inhibition in both NPY and VIP neurons, suggesting that T-stellate afferents can recruit local inhibitory circuits in the IC. To investigate how T-stellate cells influence frequency tuning and AM selectivity in the IC, we will make in-vivo single-unit recordings from IC neurons before and after silencing T-stellate inputs using chemogenetics with the inhibitory receptor hM4Di. In preliminary experiments, we have validated our chemogenetic approach by showing that co-expression of hM4Di and the excitatory opsin Chronos in T-stellate cells enables us to reduce the amplitude of light-evoked EPSPs in IC neurons with an hM4Di agonist. The overall objective of this proposal is to determine differences in the prevalence, dynamics, and pharmacology of T-stellate cell inputs to NPY and VIP neurons, and to determine how T-stellate input influences frequency tuning and AM coding in vivo. In Aim 1, we will determine the prevalence, short-term plasticity, and receptor pharmacology of T-stellate input to NPY and VIP neurons in vitro using whole cell recordings in IC slices. In Aim 2, we will determine how T-stellate neurons shape frequency tuning and AM coding in the IC by selectively inhibiting T-stellate with chemogenetics while recording from IC neurons. The expected results will provide direct evidence about how a specific source of ascending input to the IC supports the processing of auditory cues that are important for understanding speech and other vocalizations.

下丘（IC）是听觉系统的中脑中枢，是控制听觉活动的重要中枢