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

 描述(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。反过来，感受器和传入细胞从起源于脑干的传出纤维接受双边输入。到目前为止，传出通路的功能仍然难以捉摸。有人认为，传出神经可能提供了有关两侧活动失衡的信息，并在前庭代偿中发挥了作用。具体地说，传出主要影响带有花盏终末的传入神经元的活动，它完全覆盖了前庭毛细胞的基底外侧壁，并提供了一种仅存在于前庭周围的独特形式的突触。此外，有两种主要类型的传出纤维，胆碱能和GABA能。然而，关于这两条传出通路对前庭传入感觉编码的神经支配模式、突触特性、受体类型和差异效应，几乎一无所知。本研究的目的是研究由这两条通路的传出输入所介导的传入反应特性的变化及其潜在的细胞机制。这一假说得到了初步结果的支持，即传出输入将传入的放电特性和反应模式从时相改变为强音。体外实验将从细胞水平研究M胆碱型乙酰胆碱受体(MAChR)对肾盏膜特性的影响。初步数据表明，mAChRs的激活导致由花萼中存在的钾通道活动的变化所介导的紧张性传入反应的转变。此外，还将在体外研究GABA能传出输入对花萼终末细胞膜特性的影响。初步结果表明，约50%的花瓣不接受胆碱能传出，而可能接受GABA能传入。最后，我们将研究这两条传出通路对活体动物旋转运动时传入纤维放电特性的影响。 (活体内)。本方案中的实验结果可以为我们对该示例感觉系统中感觉编码的反馈调制的理解提供一个飞跃。这将是未来对警觉行为动物的研究的基础，以便将神经元和行为测量联系起来，以及研究传出输入在前庭代偿中的可能作用。

 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.