GLUTAMATE AND PREFRONTAL CORTEX FUNCTION

大量的证据表明，在精神分裂症的病理生理学中，前额叶皮层的功能不正常。虽然许多研究结果已经描述了单胺能和胆碱能投射到前额叶皮层在与该区域相关的认知功能中的作用，但最普遍的前额叶皮层传入（即含有谷氨酸作为其神经递质的投射）在前额叶皮层的记忆、注意和其他关联功能中的参与程度尚未得到很好的表征。 考虑到最近的一些研究结果表明，精神分裂症的谷氨酸能异常，这是当务之急，更多地了解谷氨酸受体在认知功能中的作用，是相关的精神分裂症神经病学。 独立科学家奖（K02）申请中提出的研究涉及表征谷氨酸受体在调节与精神分裂症病理生理学相关的前额叶皮层相关功能中的作用。 该奖项将允许申请人尽最大努力实现上述研究目标，这需要接受适当的培训，以便在她的实验室中建立与精神分裂症相关的认知功能障碍的不同方面直接相关的行为范式，并类似于精神分裂症患者表现出损害的临床测试。 考虑到目前精神分裂症的治疗模式，即，用抗多巴胺能药物治疗不能有效地治疗与这种疾病相关的认知缺陷，理解前额叶皮层的关联功能的神经化学基础将有助于开发用于治疗精神分裂症的新的药理学策略。

A plethora of evidence has implicated the improper functioning of the prefrontal cortex in the pathophysiology of schizophrenia. While numerous findings have described a role for monoaminergic and cholinergic projections to the prefrontal cortex in the cognitive functions associated with this region, the extent of the involvement of the most prevalent prefrontal cortex afferents, namely those projections that contain glutamate as their neurotransmitter, in mnemonic, attentional, and other associative functions of the prefrontal cortex has not been well characterized. Considering that a number of recent findings are suggestive of glutamatergic abnormalities in schizophrenia, it is imperative that more be learned about the role of glutamate receptors in cognitive functions that are relevant to schizophrenic symptomatology. The research proposed in this request for an Independent Scientist Award (K02) involves characterizing the contribution of glutamate receptors in regulating those associative functions of the prefrontal cortex that are relevant to the pathophysiology of schizophrenia. This award will allow the applicant to devote maximal effort to the above research objectives which entails receiving appropriate training in order to establish in her laboratory behavioral paradigms that have direct relevance to different aspects of the cognitive dysfunctions associated with schizophrenia and that are analogous to clinical tests at which patients with schizophrenia show an impairment. Considering that the present mode of therapy for schizophrenia, i.e., treatment with antidopaminergic drugs, does not effectively treat cognitive deficits associated with this disorder, an understanding of the neurochemical basis of associative functions of the prefrontal cortex will help in the development of novel pharmacotherapeutic strategies for the treatment of schizophrenia.