Differential modulation of response properties of vestibular afferents by cholinergic and GABAergic efferents.

胆碱能和 GABA 能传出神经对前庭传入神经反应特性的差异调节。

• 批准号: 9185967
• 负责人: Soroush Sadeghi Ghandehari
• 金额: $ 15.95万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9185967
• 关键词: Address; Affect; Agonist; Animals; Area; Bilateral; Brain; Brain Stem; Cholinergic Antagonists; Cholinergic Fibers; Code; Complement; Data; Detection; Drug usage; Efferent Pathways; Electrophysiology (science); Epithelium; Feedback; Fiber; Financial compensation; Frequencies; Functional disorder; Future; G-substrate; GTP-Binding Protein alpha Subunits, Gs; Ganglia; Goals; Head Movements; Immunohistochemistry; In Vitro; Intraperitoneal Injections; Label; Light; Mammals; Measures; Mediating; Membrane; Motion Sickness; Movement; Mus; Muscarinic Acetylcholine Receptor; Muscarinic Antagonists; Nerve; Neurons; Pathologic; Pathway interactions; Patients; Pattern; Peripheral; Pharmaceutical Preparations; Pharmacology; Phase; Play; Potassium; Potassium Channel; Property; Rattus; Rest; Rhodopsin; Role; Rotation; Seizures; Sensory; Side; Signal Transduction; Stimulus; Synapses; System; Testing; Therapeutic; Type II Hair Cell; Vestibular Hair Cells; Vestibular Nerve; Vestibular ganglion; afferent nerve; base; behavior measurement; cholinergic; experimental study; extracellular; genetic approach; improved; in vivo; knockout animal; nerve supply; optogenetics; patch clamp; public health relevance; receptor; response; sensory system; vestibular pathway; voltage; wortmannin

 DESCRIPTION (provided by applicant): Vestibular receptors encode information about head movements and send these signals through the vestibular nerve to the brain stem. In turn, receptors and afferents receive bilateral inputs from efferent fibers that originate in the brain stem. To date, the function of the efferent pathway has remained elusive. It has been suggested that efferents might provide information regarding imbalance in the activity on the two sides and play a role in vestibular compensation. In particular, efferents mainly affect activity of afferent with calyx terminals, which completely cover the basolateral walls of vestibular hair cells and provide a unique form of synapse present only in the vestibular periphery. Furthermore, there are two main types of efferent fibers, cholinergic and GABAergic. However, almost nothing is known regarding the innervation patterns, synaptic properties, receptor types, and differential effects of the two efferent pathways on vestibular afferent sensory coding. The goal of the present proposal is to investigate changes in afferent response properties mediated by efferent inputs from these two pathways and the underlying cellular mechanisms. The hypothesis, supported by preliminary results, is that efferent inputs change the firing properties and response patterns of afferents from phasic to tonic. The effect of muscarinic acetylcholine receptors (mAChR) on calyx membrane properties will be studied at the cellular level in vitro. Preliminary data suggest that activation of mAChRs results in a shift to tonic afferent responses mediated by changes in potassium channel activities present in calyces. The effect of GABAergic efferent inputs on membrane properties of calyx terminals will also be investigated in vitro. Preliminary results suggest that ~50% of calyces do not receive cholinergic efferents and might receive GABAergic inputs. Finally, the effect of the two efferent pathways will be studied on firing properties of afferent fibers in response to rotational movements in live animals (in vivo). Results of the experiments in this proposal can provide a leap in our understanding of feedback modulation of sensory coding in this example sensory system. This will be the basis for future studies in alert behaving animals in order to correlate neuronal and behavioral measures as well as studying the possible role of efferent inputs in vestibular compensation.

 描述（由申请人提供）：前庭感受器编码有关头部运动的信息，并通过前庭神经将这些信号发送到脑干，而感受器和传入神经则接收来自脑干的传出纤维的双边输入。传出通路的功能仍然难以捉摸，有人认为传出神经可能提供有关两侧活动不平衡的信息，并在前庭代偿中发挥作用，特别是传出神经。主要影响萼末端传入神经的活动，其完全覆盖前庭毛细胞的基底侧壁，并提供仅存在于前庭周边的独特形式的突触此外，传出纤维有两种主要类型：胆碱能纤维和 GABA 能纤维。关于神经支配模式、突触特性、受体类型以及两种传出通路对前庭传入感觉编码的差异作用几乎一无所知。目前的提议是研究由这两种途径的传出输入介导的传入反应特性的变化以及潜在的细胞机制，初步结果支持的假设是传出输入改变了传入神经的放电特性和反应模式从阶段性到强直性。毒蕈碱乙酰胆碱受体 (mAChR) 对萼膜特性的影响将在体外细胞水平上进行研究。初步数据表明 mAChR 的激活。导致肾盏中存在的钾通道活性变化介导的强直性传入反应的转变。还将在体外研究 GABA 能传出输入对萼末端膜特性的影响，初步结果表明约 50% 的肾盏不接收。最后，将研究这两种传出通路对响应旋转运动的传入纤维发射特性的影响。在活体动物中 （体内）。本提案中的实验结果可以使我们对这个示例感觉系统中感觉编码的反馈调制的理解发生飞跃，这将成为未来对警觉行为动物进行研究的基础，以便将神经和行为联系起来。措施以及研究传出输入在前庭补偿中的可能作用。