Center-surround functional organization and respiratory modulation of lateral inh

描述（由申请人提供）：气味识别在整个嗅球（OB）肾小球的活性空间分布中编码。 肾小球是灯泡中的基本计算元件，每个肾小球接收来自单一类别的嗅觉受体神经元的前馈输入。 然而，特定刺激的激活模式，即气味图，可以通过灯泡的内在电路显着改变。 例如，已经表明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，灯泡的内在电路如何将气味映射到最终传递到嗅觉皮层的刺激表征中。 这个建议的目标是阐明内在的电路组织和机制，负责塑造OB的空间表征的气味。 侧抑制（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。 有两种主要的模型侧抑制在球。 最近的一些研究表明，LI在灯泡是组织在一个中心环绕的方式，而其他人认为，LI在OB是距离无关，并遵循稀疏的网络组织。 另一个复杂性是，在灯泡LI表现出复杂的时间动态，可以通过呼吸调制。 然而，到目前为止，无论是这些抑制电路的功能组织或呼吸的时间调制已在体内进行了研究。 为了了解气味图的感觉感知的电路机制，需要确定OB中LI的组织和调制。 该建议旨在通过关注两个参数来表征OB中的LI：距离和呼吸相位。 距离研究的结果将阐明在灯泡的侧抑制的空间组织和探索的可能性，一个中心-周围的抑制网络作为气味地图处理的基础。 呼吸相位调制的研究将有重要的意义，鼻后气味的加工在感觉的味道。 当口腔中的挥发物在呼气期间激活嗅觉通路时，鼻后处理发生。 这些研究将提供第一个功能的证据呼吸相位依赖性增强鼻后加工的基础上感知的味道。 综上所述，拟议研究的结果将促进我们对OB网络如何处理和调制气味图的理解。 公共卫生相关性：本研究旨在探讨嗅球在处理与感知嗅觉刺激时的组织与回路机制。 OB中的处理在许多人类疾病中起着重要作用，包括肥胖和嗅觉丧失（嗅觉丧失）-OB也是最早显示阿尔茨海默氏症和帕金森氏症迹象的大脑区域之一。 对嗅球的功能组织和电路机制的更深入了解将为理解这些疾病的嗅觉成分奠定基础。 这些研究的相关性福尔斯“2010年健康人群”目标的优先领域，特别是目标ENT_VLS HP 2020 -18。

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.