Synaptic Processing in the Olfactory System

描述（由申请人提供）：无论是早晨咖啡的香气还是情人的香味，嗅觉都是日常生活的重要特征。我们研究的长期目标是了解嗅觉信息在哺乳动物大脑中是如何处理的。为了解决这个问题，我们研究了嗅球和嗅皮层中神经元回路和突触的特性，这是大脑中处理嗅觉信息的第一个部位。我们的统一假设是，了解嗅觉回路的突触机制对于揭示大脑如何编码我们的嗅觉非常重要。实验采用大鼠梨状前皮质的体外脑切片制备。我们还使用了一种新的切片制备，其中嗅球仍然附着在皮层上。梨状皮质锥体细胞和中间神经元将使用红外差分干涉光学可视化。我们将使用全细胞膜片钳记录和细胞内钙离子浓度成像来研究这些细胞。具体目标1提出了表征的基本机制，从嗅球到皮层的感觉信息的传输。我们假设单个二尖瓣细胞可以与梨状锥体细胞建立强连接，并且相对较少的二尖瓣细胞输入的突触整合是梨状皮质中特征检测的基础。具体目标2提出研究梨状皮质中局部抑制回路在塑造突触整合中的作用。我们假设，前馈和反馈抑制性中间神经元调节突触整合和尖峰输出在生理相关模式的嗅球输入。具体目标3提出使用嗅球-梨状皮质切片中的细胞活性成像来研究群体编码。我们假设锥体细胞活动的时间和空间模式可以编码有关嗅觉输入在嗅球中的时间和定位的信息，这些实验将为大脑嗅觉的突触机制提供新的见解。

DESCRIPTION (provided by applicant): Whether it be the aroma of our morning coffee or the scent of a lover, the sense of smell is a critical feature of daily life. The long-term objective of our research is to understand how olfactory information is processed in the mammalian brain. To address this question, we study the properties of neuronal circuits and synapses in the olfactory bulb and olfactory cortex, which are the first sites in the brain where olfactory information is processed. Our unifying hypothesis is that understanding the synaptic mechanisms of olfactory circuits is important for revealing how the brain encodes our sense of smell. The experiments proposed employ an in vitro brain slice preparation of the rat anterior piriform cortex. We also use a novel slice preparation in which the olfactory bulb remains attached to the cortex. Piriform cortex pyramidal cells and interneurons will be visualized using infrared differential interference optics. We will study these cells using whole-cell patch clamp recording and imaging of intracellular calcium concentration. Specific Aim 1 proposes to characterize the fundamental mechanisms governing the transfer of sensory information from the olfactory bulb to the cortex. We hypothesize that individual mitral cells can make strong connections onto piriform pyramidal cells and that the synaptic integration of relatively few mitral cell inputs underlies feature detection in piriform cortex. Specific Aim 2 proposes to investigate the role of local inhibitory circuits in shaping synaptic integration in piriform cortex. We hypothesize that feedforward and feedback inhibitory interneurons regulate synaptic integration and spike output during physiologically relevant patterns of olfactory bulb input. Specific Aim 3 proposes to investigate population coding using imaging of cell activity in olfactory bulb-piriform cortex slices. We hypothesize that temporal and spatial patterns of pyramidal cell activity can encode information regarding the timing and localization of olfactory input in the olfactory bulb.These experiments will provide new insight into the synaptic mechanisms underlying olfaction in the brain.