Intraglomerular Lateral Inhibition in the Mouse Olfactory Bulb

描述（申请人提供）：嗅觉系统是研究神经回路和功能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核心问题是，在感觉信息编码中，信号尖峰的模式（而不仅仅是信号尖峰的速率）涉及到何种程度。近年来，这一问题在嗅觉系统中引起了相当大的关注。我们在本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。尽管多年来人们一直在研究刺激时间可靠性和精确性的机制和功能，但很少或没有研究关注抑制在产生准确可靠的刺激时间中的作用。显然，兴奋性神经元的时间编码将需要中间神经元的合作，而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，我们发现肾小球刺激导致颗粒细胞的长潜伏期和长时间放电，表明颗粒细胞的活性在单次刺激后的几秒钟内进化。这种持久的抑制对于嗅球中神经元活动的进化至关重要。了解其产生和调节的机制对于理解球茎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的假设，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性时间。

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.