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。肾小球是球茎中基本的计算元素，每个肾小球接受来自单一类别嗅觉受体神经元的前馈输入。然而，特定刺激的激活模式，如气味地图，可以被灯泡的内在电路显著改变。例如，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激活。嗅觉系统中一个关键的、尚未解决的问题是，脑球的内在回路是如何将气味地图提炼成最终传递到嗅觉皮层的刺激表征的。本提案的目标是阐明负责塑造OB对气味的空间表征的内在回路组织和机制。侧抑制（LI）被认为在这一过程中起关键作用。LI是两个或多个神经元池相互抑制的能力。球茎侧抑制主要有两种模式。最近的一些研究表明，鳞茎中的LI以中心环绕的方式组织，而另一些研究则认为OB中的LI是距离无关的，遵循稀疏的网络组织。另一个复杂性是，球茎中的LI表现出复杂的时间动态，可以通过呼吸调节。然而，迄今为止，这些抑制回路的功能组织或呼吸对其时间调节都没有在体内进行过研究。为了了解嗅觉图的感觉知觉背后的电路机制，需要确定OB中LI的组织和调节。该建议旨在通过关注两个参数来表征OB中的LI：距离和呼吸期。距离研究的结果将阐明球茎中横向抑制的空间组织，并探索中心-环绕抑制网络作为气味地图处理基础的可能性。呼吸相位调节的研究对后鼻嗅觉的味觉处理具有重要意义。当呼气时，口腔中的挥发物激活嗅觉通路时，就会发生鼻后加工。这些研究将提供第一个功能证据，证明呼吸相依赖性增强后鼻处理是感知风味的基础。综上所述，这些研究的结果将促进我们对OB网络如何处理和调节气味地图的理解。

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.