CELLULAR PHARMACOLOGY AND PHYSIOLOGY OF SEPTAL NEURONS

背外侧隔核（DLSN）是一个完整的环节， 隔海马通路（DLSN -内侧隔-Broca斜角带， 海马- DLSN）。 尽管早期的解剖学研究 证明了它在这一途径中的重要地位， DLSN内神经元的数量尚不清楚。 我们利用体外 大鼠脑切片制备，以记录DLSN的细胞内 为了提供关于生理的基本信息， 药理学和解剖学特性。 我们对鹅膏蕈氨酸的工作和病变研究支持了我们最初的观点 假设DLSN可以作为诱导位点， 维持和表达θ节律。 这项研究将测试四个假设，这表明细胞机制 来解释DLSN中θ节律的诱导。 四个具体目标 将被处理来测试这些假设中的每一个：1）确定是否 胆碱能或GABA能受体的特定亚型可以诱导θ 通过调节特定类型的电压依赖性电导来调节节律 DLSN神经元; 2）确定是否激活胆碱能或GABA能 受体亚型可在DLSN中产生去抑制作用， theta节律; 3）表征调节非- 可以诱导θ节律的比阳离子电导;以及4） 描述代谢性兴奋性氨基酸的药理学特征 受体，其可以诱导DLSN中的LTP和可能的θ节律。 我们认为，θ节律功能正常，以促进（激励） 一个人适应（可塑性），并促进和调解这种 复杂的行为如学习和记忆。 如果θ节律不是 过分地表达或被过分地表达，如在不寻常的情绪下 环境，例如压力;或疾病状态，例如，精神分裂症; 或作为衰老过程的病理学，例如痴呆;或作为 药物滥用;可能存在三个主要递质系统的不平衡， 即GABA能、胆碱能和兴奋性氨基酸释放。 每一个传递系统都与θ节律有关 活动 这种不平衡的结果是， 促进正常行为的发生。 这项研究将提供重要的基本信息， 适用于心理健康的临床问题，因为修改 θ节律和隔神经元活动与这两种情况有关。 正常和异常的情绪表达，以及正常和 异常的认知过程 可能受益的特定精神障碍 包括：精神分裂症、焦虑症、抑郁症、痴呆症、老年痴呆症 疾病和癫痫。

The dorsolateral septal nucleus (DLSN) is an integral link in the septohippocampal pathway (DLSN - Medial septum-Diagonal Band of Broca - hippocampus - DLSN). Although earlier anatomical studies had demonstrated its essential position in this pathway, the functional roles of neurons within the DLSN were unclear. We have utilized an in vitro brain slice preparation from rats to record intracellularly from the DLSN in order to provide fundamental information about the physiological, pharmacological, and anatomical properties of individual DLSN neurons. Our work and lesion studies with ibotenic acid support our original hypothesis that the DLSN may serve as site for the induction, maintenance, and expression of theta rhythm. This study will test four hypotheses which suggest cellular mechanisms to explain the induction of theta rhythm in the DLSN. Four specific aims will be addressed to test each of these hypotheses: 1) determine whether specific subtypes of cholinergic or GABAergic receptors can induce theta rhythm by regulation of voltage-dependent conductances on specific types of DLSN neurons; 2) determine if activation of cholinergic of GABAergic receptor subtypes can produce disinhibition in the DLSN and the induction of theta rhythm; 3) characterize the subtypes that modulate a non- specific cationic conductance which can induce theta rhythm; and 4) characterize the pharmacology of a metabotropic excitatory amino acid receptor which can induce LTP and possibly theta rhythm in the DLSN. We suggest that theta rhythm functions normally to facilitate (motivate) an individual to adapt (plasticity) and to facilitate and mediate such complex behaviors as learning and memory. If theta rhythm is not expressed or is expressed excessively, as under unusual emotional circumstances, e.g. stress; or in disease states, e.g., schizophrenia; or as a pathology of the aging process, e.g. dementia; or as a result of drug abuse; there may be an imbalance of three major transmitter systems, namely, GABAergic, cholinergic, and excitatory amino acid releasing. Each of these transmitter systems has been implicated in theta rhythm activity. As a result of this imbalance, aberrant behavior, rather than facilitation of normal behavior, occurs. This study will provide important basic information that may be applicable to clinical problems in mental health, since modification of theta rhythm and septal neuronal activity have been implicated in both normal and abnormal expressions of our emotions and in both normal and abnormal cognitive processes. Specific mental disorders that may benefit include: schizophrenia, anxiety, depression, dementia, Alzheimer's disease, and epilepsy.