Circuit analysis in the olfactory cortex.

描述(由申请人提供)：拟议项目的主要目标是了解嗅觉系统中皮质处理的基本机制及其在癫痫发作启动中的作用。这项工作将专门研究嗅皮层中可能与癫痫发生有关的三条突触通路。用前嗅核和梨状皮质锥体细胞的全细胞膜片钳技术研究嗅球传入刺激的反应。配对记录将被用来研究被研究的皮质区域(包括重要的抑制输入)内和之间的细胞与免疫化学和共聚焦成像的相互作用，以补充电生理结果。嗅球中的两种主要神经元投射到嗅皮层：簇状细胞和二尖瓣细胞。簇状细胞投射到孤束核和梨状腹侧前皮质，而二尖瓣细胞投射到整个嗅皮层。虽然簇状细胞和二尖瓣细胞携带着关于嗅觉世界的不同信息，但其生理反应和功能意义尚不清楚。我们将在大脑皮层分离对这两种类型输入的反应。APCvr与极易引发强直-阵挛发作的皮层相互连接，从而提出簇状细胞输入在梨状皮质癫痫发作的启动中起特殊作用的假说。APCvr从AON接收前馈输入。关键的是，AON前馈兴奋直接与梨状前部锥体细胞的胞体相邻，而嗅球终末位于远端顶端树突上。因此，似乎AON输入，而不是嗅球输入，可能是这个致痫脑区的驱动输入。在刺激梨状皮质锥体细胞的Aon输入过程中的记录将有助于详细研究这种以前未被探索的突触联系。APCvr中未见枝形吊灯细胞的轴突末梢，也未见CCK阳性篮状胞体和末梢。我将研究梨状皮质中这些抑制性神经元对突触的影响。研究与公共卫生的相关性嗅觉系统的皮质被认为是引发某些类型癫痫发作的重要部位。研究该区域细胞之间的感觉输入和突触联系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了解。

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.