Cholinergic modulation of olfactory bulb glomerular sensitivity

嗅球肾小球敏感性的胆碱能调节

• 批准号: 8883797
• 负责人: MAX L FLETCHER
• 金额: $ 36.82万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2020-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8883797
• 关键词: Acetylcholine; Address; Affect; Alzheimer' s Disease; Arousal; Attention; Behavior; Behavioral; Behavioral Assay; Calcium; Cell Nucleus; Cells; Code; Cues; DDX26 gene; Data; Detection; Diagnosis; Diagonal Band Nucleus; Diagonal Band of Broca; Disease; Functional disorder; Goals; Human; Image; Impaired cognition; In Vitro; Individual; Learning; Limb structure; Maps; Mediating; Memory; Mus; Muscarinic Acetylcholine Receptor; Muscarinics; Neurons; Nicotinic Receptors; Odors; Olfactory Learning; Output; Parkinson Disease; Pattern; Perception; Peripheral; Pharmacology; Population; Process; Property; Regulation; Reporter; Reporting; Role; Sensory; Sensory Process; Site; Staging; Stimulus; Structure; System; Testing; Time; Transgenic Mice; Work; basal forebrain; base; calcium indicator; cell type; cholinergic; cholinergic neuron; conditioning; improved; in vivo; insight; nervous system disorder; neuronal circuitry; novel; olfactory bulb; olfactory sensory neurons; postsynaptic; presynaptic; public health relevance; receptive field; receptor; relating to nervous system; research study; response; sensory cortex; sensory input; sensory stimulus; two-photon

 DESCRIPTION (provided by applicant): The overall goal of this project is to directly test how cholinergic input from the nucleus of the horizontal limb of the diagonal band of Broca (HDB) alters olfactory bulb (OB) glomerular circuits and how this modulation ultimately affects odor coding, perception, and learning. We will use of both wide-field and 2-photon in vivo and in vitro calcium imaging in mice expressing genetically encoded indicators of neuronal activity in defined OB cell types, to test the novel overarching hypothesis that synaptically-released acetylcholine bidirectionally modulates mitral/tufted cell odor responses as a function of the prevailing odor intensity. We further test the hypothesis that this modulation is due to opposing muscarinic and nicotinic receptor actions on inhibitory periglomerular cells that differentially regulate the strength of presynaptic inhibition of olfactory sensory neuron input to the glomeruli. Using imaging and well characterized olfactory-mediated behaviors, we will also investigate how this cholinergic modulation of the glomerular odor representation affects odor perception and learning. Specifically, we test the hypotheses that HDB-evoked acetylcholine release in the OB: (1) enhances olfactory sensitivity, (2) dishabituates odor responses adapted at the peripheral olfactory sensory neuron level and (3) is critical for associative olfactory learning. By investigating receptor type-specific cholinergic modulation in morphologically- and physiologically-distinct neuron types at both the population and single cell levels, the experiments of this proposal will for the first time elucidate how cholinergic modulation of neural odor responses in the OB impacts olfactory perception and learning behaviorally. The overall findings will dramatically advance our understanding of how acetylcholine modulates sensory representation, odor coding, perception and behavior.

 描述（由申请人提供）：本项目的总体目标是直接测试来自Broca对角带水平肢核（HDB）的胆碱能输入如何改变嗅球（OB）肾小球回路，以及这种调制最终如何影响气味编码，感知和学习。我们将使用宽场和双光子在体内和体外钙成像在小鼠中表达基因编码的神经元活动的指标，在定义的OB细胞类型，以测试新的总体假设，即突触释放的乙酰胆碱双向调节二尖瓣/簇状细胞的气味反应作为一个功能的主要气味强度。我们进一步测试的假设，这种调制是由于反对毒蕈碱和烟碱受体对抑制性肾小球周围细胞的作用，差异调节的嗅觉感觉神经元输入到肾小球的突触前抑制的强度。 使用成像和良好的嗅觉介导的行为，我们也将调查如何这种胆碱能调节肾小球气味代表影响气味感知和学习。具体来说，我们测试的假设，HDB诱发的乙酰胆碱释放在OB：（1）增强嗅觉灵敏度，（2）disabituates气味反应适应在外周嗅觉感觉神经元水平和（3）是关键的联想嗅觉学习。通过在群体和单细胞水平上研究形态学和生理学上不同的神经元类型中受体类型特异性胆碱能调节，该提议的实验将首次阐明神经元的胆碱能调节是如何被调节的。 嗅球中的气味反应影响嗅觉感知和学习行为。整体研究结果将极大地推进我们对乙酰胆碱如何调节感觉表征，气味编码，感知和行为的理解。