NICOTINIC MECHANISMS IN SENSORY NEOCORTEX

描述（改编自申请人的摘要）：尼古丁是世界上使用最广泛的成瘾物质。在发达国家，以吸烟形式滥用尼古丁导致许多慢性疾病和近20%的死亡。尼古丁成瘾的机制已经得到了很好的研究。然而，尼古丁的行为效应与其身体成瘾特性不同，这有助于它的流行。尼古丁据说可以提升情绪和唤醒，减轻疼痛，提高注意力，工作记忆和感官信息的快速处理。尼古丁这些作用的机制知之甚少。大脑中的尼古丁受体最近被认为与家族性癫痫和其他神经和精神疾病有关，具有尼古丁活性的药物可能在治疗阿尔茨海默病和帕金森病方面具有潜力。这项计划的目标是研究尼古丁对前脑，特别是感觉新皮层的影响的细胞机制。新皮层及其连接占人脑体积的80%，对正常的感觉、运动、记忆和认知至关重要。尼古丁对大脑皮层的直接作用可能在药物对行为的多种影响中起着重要作用。尼古丁与神经元烟碱乙酰胆碱受体结合：在新皮层中，神经元烟碱乙酰胆碱受体在皮层的输入（即丘脑皮层）突触上以及在一些抑制性神经元和锥体神经元上丰富。本研究的目的是验证以下假设：尼古丁和特定神经元尼古丁乙酰胆碱受体的激活会改变新皮质输入突触的强度和动力学，调节突触抑制和抑制性神经元，从而系统地改变新皮质的方式转换来自丘脑的感觉信息。将在大鼠的躯体感觉系统中进行体外和体内实验。一个正式的计算模型将被用来了解尼古丁对神经元和突触的影响如何导致新皮层网络的复杂但可预测的改变，从而改变感觉。

DESCRIPTION (Adapted From The Applicant's Abstract): Nicotine is the world's most widely used addictive substance. Nicotine abuse, in the form of smoking, causes many chronic diseases and almost 20% of the deaths in developed countries. The mechanisms of nicotine's addictiveness are well studied. However nicotine has behavioral effects distinct from its physically addictive qualities, and these contribute to its popularity. Nicotine is said to elevate mood and arousal, reduce pain, and improve attention, working memory, and the rapid processing of sensory information. The mechanisms for these effects of nicotine are very poorly understood. Nicotine receptor in the brain have recently been implicated in a familial form of epilepsy and other neurological and psychiatric disorders, and drugs with nicotinic activity may have potential in the treatment of Alzheimer's and Parkinson's disease. The goal of this proposal is to study the cellular mechanisms of nicotine's effects on the forebrain, in particular the sensory neocortex. Neocortex and its connections comprise 80% of human brain volume, and it is essential for normal sensation, movement, memory and cognition. Nicotine's direct action on neocortex probably plays a major role in the drug's diverse effects on behavior. Nicotine binds to neuronal nicotinic acetylcholine receptors : in neocortex neuronal nicotinic acetylcholine receptors are abundant on the input (I.e. Thalamocortical) synapses to the cortex, and on some inhibitory and pyramidal neurons. The aims of this investigation are to test the hypothesis that nicotine, and the activation of specific neuronal nicotinic acetylcholine receptors, alters the strength and dynamics of input synapsis to the neocortex, modulates synaptic inhibition and inhibitory neurons, and thus systematically changes the way the neocortex transforms sensory information from the thalamus. Experiments will be performed in vitro and in vivo in the somatosensory system of rats. A formal computational model will be used to understand how nicotine's effects on neurons and synapses lead to complex but predictable alterations of the neocortical network, and thus alter sensation.