Circuit analysis in the olfactory cortex.

描述（由申请人提供）：拟议项目的广泛目标是了解嗅觉系统中皮层处理的基本机制及其在癫痫发作中的作用。这项工作将专门解决三个突触通路在嗅觉皮层可能有助于癫痫。采用全细胞膜片钳技术研究嗅球刺激对前嗅核和梨状皮质锥体细胞的反应。配对记录将用于研究正在研究的皮质区域内和之间的细胞相互作用（包括重要的抑制性输入）以及免疫化学和共聚焦成像，以补充电生理结果。嗅球中有两种主要神经元投射到嗅皮质：簇状细胞和僧帽细胞。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觉皮质。虽然簇状细胞和僧帽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。我们将在皮层中区分对这两种输入的反应。aPCvr与对强直-阵挛性癫痫发作的起始高度敏感的底层皮层紧密连接，导致了簇状细胞输入在梨状皮层中癫痫发作的起始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前馈兴奋终止直接相邻的锥体细胞的细胞体在前梨状，而嗅球终端的远端顶端树突。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。梨状皮质锥体细胞在刺激他们的AON输入记录将允许详细研究这种以前未探索的突触连接。aPCvr不存在枝形细胞的轴-轴盒状末梢和胆囊收缩素阳性篮状细胞体和末梢。我将研究梨状皮质中这些抑制性神经元的突触影响。研究与公共卫生的相关性嗅觉系统的皮层是已知的是一个重要的网站为启动某些类型的癫痫发作。对这一区域的感觉输入和细胞之间的突触连接的研究将有助于理解癫痫发作启动的机制。长期致力于开发更好的癫痫治疗方法，关键取决于对潜在电路的理解。

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.