Intraglomerular Lateral Inhibition in the Mouse Olfactory Bulb

描述(申请人提供)：嗅觉系统是一个模型系统，用于研究神经元电路和功能的许多方面。在包括嗅觉系统在内的许多感觉系统中出现的一个中心问题是，感觉信息的编码在多大程度上涉及到尖峰模式(而不仅仅是尖峰速度)。近年来，这一问题在嗅觉系统中引起了相当大的关注。我们在这项提案中描述的工作研究了可能使这种时间编码成为可能的细胞和电路水平的机制，重点是颗粒细胞介导的抑制在调节二尖瓣细胞放电中的作用。尽管多年来在许多大脑区域对峰时间可靠性和精确度的机制和功能进行了研究，但很少或根本没有工作集中在抑制在产生准确可靠的峰时间方面的作用。显然，兴奋性神经元放电的时间编码将需要中间神经元的合作，这种合作的性质是我们这里提出的实验的重点。通过在体外对大量嗅球颗粒细胞进行成像，我们已经表明，肾小球刺激导致颗粒细胞的长潜伏期、延长的放电，表明颗粒细胞的活动在单一刺激后的几秒钟内演变。这种持久的抑制对于嗅球神经元活动的进化至关重要。了解气味产生和调节的机制对于了解鳞茎中气味诱发活动的变化至关重要。因此，我们提出实验来评估长潜伏期、颗粒细胞介导的抑制在二尖瓣细胞激活后数百毫秒内调节二尖瓣细胞活动的时间的假设。 与公共健康相关：尽管进行了多年的工作，科学家们仍然不能理解从一个神经元发送到另一个神经元的信号的性质，以及神经活动的哪些方面是信号的一部分，而不是噪音的一部分。这项提议中的实验研究了嗅球神经元活动的时间模式的一些特征，并试图确定产生这些放电模式的细胞和电路水平的机制。这样的研究对于理解神经元活动的哪些方面涉及到从一个神经元到另一个神经元的信号是至关重要的。

DESCRIPTION (provided by applicant): The olfactory system is a model system for the study of many aspects of neuronal circuits and function. A central question that arises in many sensory systems, including the olfactory system is the extent to which patterns of spiking (as opposed to just the rate of spiking) are involved in the coding of sensory information. In recent years, considerable attention has been paid to this issue in the olfactory system. The work we describe in this proposal investigates cellular and circuit-level mechanisms that may make such temporal coding possible, focusing on the role of granule cell-mediated inhibition in regulating mitral cell firing. Despite years of work on mechanisms and function of spike time reliability and precision in many brain areas, little or no work has focused on the role of inhibition in generating accurate and reliable spike times. Clearly, temporal coding of spiking in excitatory neurons will require cooperation of interneurons and the nature of this cooperation is the focus of the experiments that we propose here. By imaging large populations of olfactory bulb granule cells in vitro we have shown that glomerular stimulation results in long latency, prolonged firing of granule cells, indicating that granule cell activity evolves over periods of seconds following a single stimulus. This long-lasting inhibition will be critical for the evolution of neuronal activity in the olfactory bulb. Understanding the mechanisms by which it is generated and regulated will be essential to understanding the transformations of odor-evoked activity in the bulb. Thus, we propose experiments to evaluate the hypothesis that long latency, granule cell mediated inhibition regulates the timing of mitral cell activity for hundreds of milliseconds following mitral cell activation. PUBLIC HEALTH RELEVANCE: Despite years of work, scientists still do not understand the nature of the signals sent from one neuron to another and what aspects of neural activity are part of the signal, vs. part of the noise. Experiments in this proposal investigate some features of the temporal patterns of neuronal activity in the olfactory bulb and seek to determine the cellular and circuit level mechanisms that generate these firing patterns. Such studies are critical for understanding which aspects of neuronal activity are involved in signaling from one neuron to the next.