LOCUS COERULEUS MODULATION OF OLFACTORY NETWORK FUNCTION

蓝斑对嗅觉网络功能的调节

• 批准号: 2128032
• 负责人: Michael Thomas Shipley
• 金额: $ 19.65万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-01 至 1998-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2128032
• 关键词: adrenergic receptor; central neural pathway /tract; evoked potentials; experimental brain lesion; gamma aminobutyrate; granule cell; hormone regulation /control mechanism; immunoelectron microscopy; laboratory rat; lateral olfactory area; locus coeruleus; neural information processing; neural inhibition; neuroanatomy; neuronal transport; neuropharmacology; neurotransmitter transport; norepinephrine; olfactory threshold; synapses; video microscopy; voltage /patch clamp

The main olfactory bulb (MOB) and piriform cortex (PC) comprise a relatively simple, well characterized, sensory neural network. Our studies have shown that 40% of all locus coeruleus (LC) neurons project to MOB where they terminate with a higher degree of laminar specificity than any other forebrain target. LC-norepinephrine (NE) inputs preferentially terminate in the granule cell layer (GCL). This layer contains granule cells which are GABAergic interneurons that control the spontaneous and sensory-evoked activity of mitral cells. The mitral cell receives olfactory neuron sensory input and relays MOB output to PC. The laminar organization of LC-NE inputs to the GCL leads to specific predictions about the cellular targets and functional modulation of bulb neurons by LC-NE synapses. Preliminary studies support these predictions. Specifically, confirmed activation of LC increases the response of identified mitral cells to sensory input. We will use EM- immunocytochemical and neurophysiological methods to directly test the hypothesis that LC-NE inputs disinhibit mitral cells by direct or indirect (presynaptic) inhibition of granule cells. We will further test the hypothesis that LC-NE activation increases the signal-to-noise (S/N) ratio of sensory throughout in MOB. Our preliminary studies show that LC also massively innervates PC. The target(s) of LC-NE terminals in PC ar unknown and will be determined by localizing NE synapses on identified PC neurons intracellularly-filled in fixed slices. In vivo and in vitro physiological studies will test the hypothesis that NE modulates PC neurons so as to preserve or enhance S/N ratio gains achieved by LC-NE modulation of MOB. The long range goal of these studies is to close the gap between global hypotheses of LC-NE function and cellular-molecular studies of NE synaptic actions by characterizing LC-NE modulation of a cortically organized, integrated sensory neural network.

主嗅球（MOB）和梨状皮层（PC）包括A 相对简单，表征良好的感觉神经网络。 我们的 研究表明，所有基因座（LC）神经元项目中有40％ 到他们以较高程度的层流特异性终止的暴民 比任何其他前脑目标。 LC-Norepinephrine（NE）输入 优先终止在颗粒细胞层（GCL）中。 这层 包含颗粒细胞，这些细胞是控制gabaergic的中间神经元 二尖瓣的自发和感觉诱发活性。 二尖瓣 接收嗅觉神经元感觉输入，并将MOB输出转移到PC。 这 LC-NE输入到GCL的层流组织导致特定 关于灯泡细胞靶标和功能调节的预测 LC-NE突触的神经元。 初步研究支持这些 预测。 具体而言，确认的LC激活增加了 鉴定出二尖瓣对感觉输入的响应。 我们将使用em- 免疫细胞化学和神经生理学方法直接测试 LC-NE输入通过直接或直接或 间接（突触前）抑制颗粒细胞。 我们将进一步测试 LC-NE激活增加了信号到噪声的假设（S/N） 暴民中的感觉比率。 我们的初步研究表明，LC也大大支配PC。 这 PC AR中LC-NE终端的目标未知，将由 将NE突触定位在已识别的PC神经元内填充的识别PC神经元上 在固定的切片中。 体内和体外生理研究将测试 NE调节PC神经元以保护或增强的假设 LC-NE调制BOB实现的S/N比率获得。 这些研究的远距离目标是缩小全球的差距 LC-NE功能和NE的细胞分子研究的假设 通过表征皮质的LC-NE调制来表征突触动作 有组织的，综合的感觉神经网络。