TEMPORAL LOBE PATHWAYS THROUGH THE DOPAMINE SYSTEM

通过多巴胺系统的颞叶通路

• 批准号: 6969029
• 负责人: JULIE L. FUDGE
• 金额: $ 27万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6969029
• 关键词: BCL2 gene /protein; Cercopithecidae; amygdala; developmental neurobiology; dopamine; dopamine receptor; electrophysiology; genetic regulation; hippocampus; immunocytochemistry; immunofluorescence technique; interneurons; neural plasticity; protein structure function; psychosis; radionuclide double label; schizophrenia; temporal lobe /cortex

DESCRIPTION (provided by applicant): Structural abnormalities of the amygdala/hippocampal complex are a consistent finding in schizophrenia. In animal models, neonatal damage to the amygdala/hippocampal complex results in adult onset dopamine (DA) dysregulation, another key feature of this illness. Maintaining the integrity of amygdala/hippocampal circuits therefore appears critical to later DA function. We have previously shown that the extended amygdala, a major output region of the amygala and other temporal lobe structures, has broad inputs to the dopamine neurons. This pathway is thus a potential route by which amygdala-hippocampal abnormalities may eventually lead to DA dysregulation. The proposed studies will examine how the amygdala and hippocampus can influence the midbrain DA system through the extended amygdala. The fact that temporal lobe injury results in DA dysregulation only later in development suggests that plastic changes eventually influence DA output. Our preliminary results show that B lymphocyte 2 protein (bcl-2), which protects cells from excitotoxic damage and also has neurotrophic effects, is highly concentrated in specific subregions of the adult primate temporal lobe. Our preliminary results show high concentrations of Bcl-2 positive cells in the extended amygdala, and in subregions of the amygdala and hippocampus associated with schizophrenia. The presence of bcl-2 in specific circuits may help to identify excitatory pathways most susceptible to plastic changes and/or excitotoxic stress in adult animals. The proposed studies will identify temporal lobe circuits that influence DA through the extended amygdala. Specifically we will: 1) identify direct amygdaloid and hippocampal inputs to the extended amygdala-DA pathway, 2) identify indirect hippocampal pathways through the amygdala that influence the extended amygdala, 3) determine whether specific amygdaloid and hippocampal input/output paths contain Bcl-2 immunoreactive cells, 4) determine the extent to which hippocampal inputs overlap amygdala subregions that project to the extended amygdala, and the extent to which this input overlaps inhibitory interneurons and bcl-2-containing cells.

描述（由申请人提供）：杏仁核/海马复合物的结构异常是精神分裂症的一致发现。在动物模型中，新生儿对杏仁核/海马复合物的损害导致成年发作多巴胺（DA）失调，这是这种疾病的另一个关键特征。因此，维持杏仁核/海马电路的完整性似乎对于后来的DA功能至关重要。我们先前已经表明，杏仁核是杏仁核和其他颞叶结构的主要输出区域，对多巴胺神经元具有广泛的输入。因此，该途径是一种潜在的途径，杏仁核 - 海马异常最终可能导致DA失调。拟议的研究将研究杏仁核和海马如何通过扩展的杏仁核影响中脑DA系统。颞叶损伤导致DA失调的事实仅在发育后的后期表明，塑料变化最终会影响DA输出。我们的初步结果表明，保护细胞免受兴奋性毒性损伤并具有神经营养作用的B淋巴细胞2蛋白（BCL-2）高度集中在成年灵长类动物颞叶的特定子区域。我们的初步结果表明，在扩展的杏仁核以及与精神分裂症相关的杏仁核和海马的子区域中，Bcl-2阳性细胞的高浓度。在特定电路中存在Bcl-2可能有助于确定成年动物中最容易受到塑性变化和/或兴奋性应激最容易受到的兴奋性途径。 拟议的研究将确定通过扩展的杏仁核影响DA的颞叶回路。具体而言，我们将：1）确定直接的杏仁核和海马输入到延长的杏仁核-da途径，2）确定通过杏仁核的间接海马途径，影响延长的杏仁核，3）3）海马输入重叠，将投射到扩展的杏仁核的杏仁核子区域以及该输入重叠抑制性中间神经元和含Bcl-2的细胞的程度。