Intraglomerular Lateral Inhibition in the Mouse Olfactory Bulb

描述（由申请人提供）：嗅觉系统是用于研究神经元回路和功能的许多方面的模型系统。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，尖峰模式（而不仅仅是尖峰速率）在感觉信息编码中的参与程度。近年来，嗅觉系统的这一问题受到了相当大的关注。我们在本提案中描述的工作调查了可能使这种时间编码成为可能的细胞和回路水平机制，重点关注颗粒细胞介导的抑制在调节二尖瓣细胞放电中的作用。尽管多年来的工作机制和功能的尖峰时间的可靠性和精确性在许多脑区，很少或没有工作集中在抑制的作用，产生准确和可靠的尖峰时间。显然，兴奋性神经元尖峰脉冲的时间编码需要中间神经元的合作，这种合作的性质是我们在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，肾小球刺激导致长潜伏期，颗粒细胞长时间放电，表明颗粒细胞活性在单一刺激后的几秒钟内演变。这种持久的抑制对于嗅球中神经元活动的演变至关重要。了解其产生和调节的机制对于理解灯泡中气味诱发活动的转变至关重要。因此，我们提出实验来评估长潜伏期，颗粒细胞介导的抑制调节二尖瓣细胞激活后数百毫秒的二尖瓣细胞活动的时间的假设。 公共卫生相关性：尽管经过多年的研究，科学家们仍然不了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。在这个建议中的实验调查嗅球神经元活动的时间模式的一些功能，并试图确定产生这些放电模式的细胞和电路水平的机制。这些研究对于理解神经元活动的哪些方面参与从一个神经元到下一个神经元的信号传递至关重要。

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.