Circuit analysis in the olfactory cortex.

嗅觉皮层的电路分析。

• 批准号: 7331907
• 负责人: Matthew J McGinley
• 金额: $ 4.1万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7331907
• 关键词: Action Potentials; Address; Anterior; Apical; Area; Automobile Driving; Axon; Brain; Brain region; Cell Communication; Cells; Cholecystokinin; Chromosome Pairing; Convulsants; Coupled; Dendrites; Development; Distal; Electric Stimulation; Epilepsy; Epileptogenesis; Feedback; Goals; Hand; Image; Imaging Techniques; Immunochemistry; Lead; Mus; Myoepithelial cell; Neurons; Olfactory Cortex; Pathway interactions; Pattern; Physiological; Play; Positioning Attribute; Prefrontal Cortex; Preparation; Primates; Process; Property; Public Health; Pyramidal Cells; Rattus; Research; Role; Seizures; Sensory; Shunt Device; Site; Slice; Smell Perception; Structure; Synapses; System; Tonic - clonic seizures; Transgenic Mice; Whole-Cell Recordings; Work; design; hippocampal pyramidal neuron; inhibitory neuron; interest; neuronal cell body; olfactory bulb; olfactory nuclei; patch clamp; piriform cortex; response; voltage clamp

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.

描述（由申请人提供）：拟议项目的总体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中的作用。这项工作将专门研究嗅觉皮层中可能导致癫痫发生的三种突触通路。前嗅核（AON）和梨状皮层皮质锥体细胞的全细胞膜片钳将用于研究对嗅球输入刺激的反应。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（包括重要的抑制输入）以及免疫化学和共聚焦成像，以补充电生理学结果。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 AON 和腹口前梨状皮层 (aPCvr)，而二尖瓣细胞投射到整个嗅觉皮层。虽然簇状细胞和二尖瓣细胞携带有关嗅觉世界的不同信息，但其生理反应和功能意义尚不清楚。我们将在皮层中分离对这两种类型的输入的响应。 aPCvr 与底层皮层相互连接，该皮层对强直阵挛性癫痫发作高度敏感，因此推测簇状细胞输入在梨状皮层癫痫发作的引发中发挥特殊作用。 aPCvr 接收来自 AON 的前馈输入。至关重要的是，AON 前馈激发直接终止于梨状前部锥体细胞的细胞体附近，而嗅球终端则位于远端顶端树突上。因此，似乎 AON 输入（而不是嗅球输入）可能是该致癫痫脑区域的驱动输入。在刺激其 AON 输入期间梨状皮层锥体细胞的记录将允许对这种先前未探索的突触连接进行详细研究。 aPCvr 中不存在吊灯细胞的轴突盒末端和胆囊收缩素阳性篮状细胞体和末端。我将研究梨状皮层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 众所周知，嗅觉系统的皮层是引发某些类型癫痫发作的重要部位。研究该区域细胞的感觉输入和突触连接将有助于理解癫痫发作的机制。对开发更好的癫痫治疗方法的长期承诺很大程度上取决于对基础电路的理解。