Feedforward inhibition in the olfactory bulb: Cellular basis of differential mitr

描述(申请人提供)：嗅球在编码嗅觉信息并将其传递到下游大脑区域方面发挥着关键作用。这项建议定义了一个实验计划，以确定为二尖瓣细胞提供抑制性输入的局部中间神经元的亚型，二尖瓣细胞是嗅球输出细胞的主要类别之一。这些抑制回路控制着该回路如何被激活和塑造二尖瓣细胞的活动。我将首先确定局部中间神经元的特殊亚型，这些神经元的轴突终末位于含有二尖瓣细胞突起的层中。除了通常研究的颗粒细胞外，嗅球中有几种相对未被探索的中间神经元亚型可以与二尖瓣细胞突触。我的初步研究表明，其中一种定向水平细胞单突触抑制二尖瓣细胞。利用全细胞膜片钳电生理学和活体双光子成像技术，在急性啮齿动物脑片上，我将定义二尖瓣细胞层附近有轴突的中间神经元的形态和电生理特性。使用可视化的配对记录，然后我将确定这些中间神经元亚型中的哪些实际上抑制了二尖瓣细胞，并确定了这种抑制的功能后果。接下来，我将通过刺激嗅觉感觉神经元轴突来触发对这些局部中间神经元的兴奋，并确定水平(和相关的)类中间神经元是由相对较少的肾小球柱(如二尖瓣和簇状细胞)激活的，还是从多个输入小球广泛整合突触输入。最后，我还将使用体外培养的 联合嗅球/梨状皮质切片制备以确定这些中间神经元是否接受来自嗅皮层的离心性输入。使用这些策略，我将确定抑制二尖瓣细胞的嗅球回路的集合，以及这种抑制如何影响二尖瓣细胞的功能。

DESCRIPTION (provided by applicant): The olfactory bulb performs a critical role in encoding olfactory information and routing it to downstream brain regions. This proposal defines an experimental plan to determine the subtypes of local interneurons that provide inhibitory input to mitral cells, one of the main classes of output cells in the olfactory bulb. These inhibitory circuts govern how the circuit is activated and sculpt mitral cell activity. I will first determine the speific subtypes of local interneurons that have axon terminals in layers containing mitral cell processes. There are several relatively unexplored interneuron subtypes in the olfactory bulb that could synapse onto mitral cells, in addition to commonly studied granule cells. My preliminary studies have suggested that one of these, oriented horizontal cells, monosynaptically inhibits mitral cells. Using whole-cell patch clamp electrophysiology and live 2-photon imaging in acute rodent brain slices, I will define the morphological and electrophysiological properties of interneurons with axonal ramifications near the mitral cell layer. Using visualized paired recordings, I will then determine which of these interneuron subtypes actually inhibits mitral cells and define the functional consequences of this inhibition. Next, I will trigger excitation onto these local interneurons by stimulating olfactory sensory neuron axons and determine whether horizontal (and related) classes of interneurons are activated by relatively few glomerular columns (like mitral and tufted cells are) or, instead, integrate synaptic input widely from multiple input glomeruli. Finally, I will also use an in vitro combined olfactory bulb/piriform cortex slice preparation to determine if these interneurons receive centrifugal input from olfactory cortex. Using these strategies, I will determine the set o olfactory bulb circuits that inhibit mitral cells and how this inhibition affects mitral cell functon.