Circuit analysis in the olfactory cortex.

描述（由申请人提供）：该项目的主要目标是了解嗅觉系统皮层处理的基本机制及其在癫痫发作中的作用。这项工作将专门研究嗅觉皮层中可能有助于癫痫发生的三个突触通路。利用前嗅核和梨状皮质皮质锥体细胞全细胞膜片钳研究嗅球输入刺激的反应。配对记录将用于研究被研究的皮层区域内和区域间细胞的相互作用（包括重要的抑制输入），免疫化学和共聚焦成像以补充电生理结果。嗅球中的两种主要神经元投射到嗅觉皮层：簇状细胞和二尖瓣细胞。簇状细胞投射到AON和腹侧前梨状皮质（aPCvr），而二尖瓣细胞投射到整个嗅皮质。虽然簇状细胞和二尖瓣细胞携带不同的嗅觉信息，但其生理反应和功能意义尚不清楚。我们将把大脑皮层对这两种输入的反应分开。aPCvr与下部皮层相互连接，下部皮层极易引发强直阵挛性癫痫发作，这导致了簇状细胞输入在梨状皮质癫痫发作中起特殊作用的假设。aPCvr接收来自AON的前馈输入。重要的是，AON前馈兴奋直接终止于梨状前部锥体细胞的细胞体附近，而嗅球末端位于远端根尖树突上。因此，似乎AON输入，而不是嗅球输入，可能是这个致癫痫脑区的驱动输入。在刺激梨状皮质锥体细胞的AON输入时的记录将允许详细研究这种以前未探索的突触连接。装饰灯细胞的轴-轴突筒状末梢和胆囊收缩素阳性的篮状细胞体和末梢在aPCvr中缺失。我将研究这些抑制神经元对梨状皮质突触的影响。研究与公共卫生的相关性嗅觉系统皮层是某些类型癫痫发作起始的重要部位。对这一区域的感觉输入和细胞间突触连接的研究将有助于理解癫痫发作的机制。长期致力于开发更好的癫痫治疗方法，关键取决于对潜在神经回路的理解。

DESCRIPTION (provided by applicant): The broad goal of the proposed project is to understand the fundamental mechanisms of cortical processing in the olfactory system and their role in seizure initiation. The work will specifically address three synaptic pathways in olfactory cortex which may contribute to epileptogenesis. Whole-cell patch-clamp of cortical pyramidal cells in anterior olfactory nucleus (AON) and piriform cortex will be used to study the response to stimulation of input from the olfactory bulb. Paired recordings will be used to study the interactions of cells within and between the cortical regions being studied (including important inhibitory inputs) and immunochemistry and confocal imaging to compliment electrophysiological results. Two types of principal neurons in the olfactory bulb project to the olfactory cortex: tufted and mitral cells. Tufted cells project to AON and ventrorostral anterior piriform cortex (aPCvr), while mitral cells project to the entirety of olfactory cortex. While tufted and mitral cells carry different information about the olfactory world, the physiological response and functional significance of this is not known. We will separate the response, in cortex, to these two types of inputs. The aPCvr is reciprocally connected to an underlying cortex which is highly susceptible to the initiation of tonic-clonic seizures, leading to the hypothesis that tufted cell input plays a special role in the initiation of seizures in piriform cortex. The aPCvr receives feedforward input from the AON. Critically, AON feedforward excitation terminates directly adjacent to the cell bodies of pyramidal cells in anterior piriform, while olfactory bulb terminals are on the distal apical dendrites. Therefore it appears that AON input, but not olfactory bulb input, may be the driving input to this epileptogenic brain region. Recordings of piriform cortical pyramidal cells during stimulation of their AON inputs will allow detailed study of this previously unexplored synaptic connection. Axo-axonic cartridge endings of chandelier cells, and cholecystokinin positive basket cell bodies and endings are absent from aPCvr. I will study the synaptic influence of these inhibitory neurons in piriform cortex. Relevance of Research to Public Health The cortex of the olfactory system is known to be an important site for the initiation of some types of epileptic seizures. Study of the sensory input to and synaptic connections between cells in this region will help understand the mechanisms that underlie seizure initiation. A long-term commitment to the development of better treatments for epilepsy depends critically on an understanding of underlying circuitry.