Center-surround functional organization and respiratory modulation of lateral inh

描述(由申请人提供)：气味识别编码在嗅球(OB)肾小球活动的空间分布中。肾小球是球的基本计算元素，每个肾小球接受来自一类嗅觉感受器神经元的前馈输入。然而，特定刺激的激活模式，即气味映射，可以被灯泡的内在电路戏剧性地改变。例如，已有研究表明，OB投射神经元，二尖瓣和簇状(MT)细胞的尖峰活动并不直接对应于局部肾小球的激活。嗅觉系统中一个关键的、悬而未决的问题是，嗅球的内在回路如何将气味映射精炼成最终传递到嗅觉皮质的刺激表示。这项建议的目的是阐明负责形成OB气味的空间表征的内在回路组织和机制。侧向抑制(LI)被认为在这一过程中起着关键作用。LI是两个或多个神经元池表现出相互抑制的能力。鳞茎中有两种主要的侧向抑制模式。最近的一些研究表明，灯泡里的李是以中心环绕的方式组织的，而另一些研究则认为，OB中的李是独立于距离的，遵循稀疏的网络组织。另一个复杂性是，灯泡中的LI表现出复杂的时间动力学，可以受到呼吸的调节。然而，到目前为止，这些抑制回路的功能组织和呼吸对它们的时间调制都没有在体内进行研究。为了理解嗅觉地图潜在的感觉回路机制，需要确定LI在OB中的组织和调制。这项建议旨在通过关注两个参数来描述OB中的LI：距离和呼吸时相。距离研究的结果将阐明球的侧抑制的空间组织，并探索中心-周围抑制网络作为气味图处理的基础的可能性。呼吸时相调节的研究将对味觉中鼻后气味的处理具有重要意义。当口腔中的挥发物在呼气时激活嗅觉通路时，就会发生鼻后加工。这些研究将为呼吸时相依赖的增强鼻后加工提供第一个功能性证据，作为感知味道的基础。综上所述，拟议的研究结果将促进我们对气味地图是如何被OB网络处理和调制的理解。 与公共健康相关：本项目旨在阐明嗅球(OB)中处理和感知嗅觉刺激的组织和回路机制。在包括肥胖和嗅觉障碍(嗅觉障碍)在内的许多人类疾病中，OB区的处理起着重要作用--OB区也是最早显示出阿尔茨海默氏症和帕金森氏症迹象的大脑区域之一。更透彻地了解OB的功能组织和回路机制将为理解这些疾病的嗅觉成分奠定基础。这些研究的相关性属于“2010年健康人”目标的优先领域，特别是ENT_VLS HP2020-18目标。

DESCRIPTION (provided by applicant): Odorant identity is encoded in the spatial distribution of activity across olfactory bulb (OB) glomeruli. Glomeruli are the fundamental computational elements in the bulb, with each glomerulus receiving feed- forward input from a single class of olfactory receptor neurons. However, the patterns of activation for specific stimuli, i.e. odor maps, can be dramatically altered by the bulb's intrinsic circuitry. For example, it has been shown that the spiking activity of the OB projection neurons, mitral and tufted (MT) cells, does not correspond directly to local glomerular activation. One critical, unresolved question in the olfactory system is how the bulb's intrinsic circuitry refines odor maps into the stimulus representation that is eventually transmitted to the olfactory cortices. The goal of this proposal is to elucidate the intrinsic circuit organizations and mechanisms responsible for shaping the OB's spatial representation of odorants. Lateral inhibition (LI) is believed to play a key role in this process. LI is the capacity of two or more neuronal pools to exhibit mutual inhibition. There are two predominant models of lateral inhibition in the bulb. Some recent studies have suggested that LI in the bulb is organized in a center-surround fashion, while others have argued that LI in the OB is distance-independent and follows a sparse network organization. An additional complexity is that LI in the bulb exhibits complex temporal dynamics and can be modulated by respiration. However, to date, neither the functional organization of these inhibitory circuits or their temporal modulation by respiration has been investigated in vivo. In order to understand the circuit mechanisms underlying sensory perception of the odor maps, both the organization and modulation of LI in the OB need to be determined. This proposal aims to characterize LI in the OB by focusing on two parameters: distance and respiratory phase. The results from the distance studies will elucidate the spatial organization of lateral inhibition in the bulb and explore the possibility of a center-surround inhibitory network as a basis for odor map processing. Studies of respiratory phase modulation will have important implications for the processing of retronasal smells in the sensation of flavor. Retronasal processing occurs when volatiles in the mouth activate the olfactory pathway during expiration. These studies will provide the first functional evidence for respiration phase-dependent enhancement of retronasal processing as a basis for the perception of flavor. Taken together, the results from the proposed studies will advance our understanding of how odor maps are processed and modulated by the OB network. PUBLIC HEALTH RELEVANCE: This project proposes to elucidate the organization and circuit mechanisms involved in processing and perceiving olfactory stimuli in the olfactory bulb (OB). Processing in the OB plays an important role in many human diseases including obesity and anosmia (inability to smell) - the OB is also one of the first brain regions to show indications of Alzheimer's and Parkinson's diseases. A more thorough knowledge of the functional organization and circuit mechanisms of the OB will form a foundation to understand the olfactory components of these diseases. The relevance of these studies falls within the priority areas in the "Healthy People 2010" objectives, specifically objective ENT_VLS HP2020-18.