Dopamine system dysregulation by the ventral subiculum as the common pathophysiological basis for schizophrenia psychosis, psychostimulant abuse, and stress.
Dopamine system dysregulation by the ventral subiculum as the common pathophysiological basis for schizophrenia psychosis, psychostimulant abuse, and stress.
复制标题
DOI：
10.1007/s12640-010-9154-6
复制
发表时间：
2010-11
影响因子：
3.7
通讯作者：
Grace, Anthony A.
中科院分区：
文献类型：
--
作者：
Grace, Anthony A.
多巴胺系统处于多种形式的调节下，并反过来提供对系统反应的有效调节。已知多巴胺神经元以多种活动状态存在。群体活动，或自发放电的多巴胺神经元的比例，是由海马体的腹侧下托控制的。相反，被认为是多巴胺系统的行为显著输出的爆发性放电是由脑干脚桥被盖驱动的。当动物暴露于行为上显著的刺激时，脚桥脑被盖会在多巴胺神经元中爆发动作电位。然而，这种爆发只发生在自发放电的多巴胺神经元群体中。这个比例是由腹侧下托调节的。因此，腹侧下托为行为显著刺激提供增益或放大因子。腹侧下托本身被认为携带着与环境相关的信息。因此，腹侧下托将根据生物体的需要和环境的特征来调节多巴胺系统的反应性。然而，这种精细调节的系统在疾病状态下可能会被破坏。在精神分裂症中，腹侧下托的神经元间调节的中断被认为导致多巴胺系统的过度兴奋，使系统处于恒定的高度警惕状态。此外，安非他明致敏和应激源似乎也会导致异常的多巴胺能驱动。这种相互作用可能是精神病事件沉淀中药物滥用和压力的风险因素的基础。另一方面，这可能表明腹侧下托是治疗甚至预防精神分裂症的有效治疗干预部位。
The dopamine system is under multiple forms of regulation, and in turn provides effective modulation of system responses. Dopamine neurons are known to exist in several states of activity. The population activity, or the proportion of dopamine neurons firing spontaneously, is controlled by the ventral subiculum of the hippocampus. In contrast, burst firing, which is proposed to be the behaviorally salient output of the dopamine system, is driven by the brainstem pedunculopontine tegmentum. When an animal is exposed to a behaviorally salient stimulus, the pedunculopontine tegmentum elicits a burst of action potentials in the dopamine neurons. However, this bursting only occurs in the portion of the dopamine neuron population that is firing spontaneously. This proportion is regulated by the ventral subiculum. Therefore, the ventral subiculum provides the gain, or the amplification factor, for the behaviorally salient stimulus. The ventral subiculum itself is proposed to carry information related to the environmental context. Thus, the ventral subiculum will adjust the responsivity of the dopamine system based on the needs of the organism and the characteristics of the environment. However, this finely tuned system can be disrupted in disease states. In schizophrenia, a disruption of interneuronal regulation of the ventral subiculum is proposed to lead to an overdrive of the dopamine system, rendering the system in a constant hypervigilant state. Moreover, amphetamine sensitization and stressors also appear to cause an abnormal dopaminergic drive. Such an interaction could underlie the risk factors of drug abuse and stress in the precipitation of a psychotic event. On the other hand, this could point to the ventral subiculum as an effective site of therapeutic intervention in the treatment or even the prevention of schizophrenia.
登录
查看更多内容
影响因子：
2.9
作者：
French, SJ;Hailstone, JC;Totterdell, S
通讯作者：
Totterdell, S
影响因子：
3
作者：
Basar-Eroglu, Canan;Brand, Andreas;Schmiedt, Christina
通讯作者：
Schmiedt, Christina
影响因子：
2.9
作者：
BADIANI, A;BROWMAN, KE;ROBINSON, TE
通讯作者：
ROBINSON, TE
影响因子：
3.3
作者：
FINLAY, JM;ZIGMOND, MJ;ABERCROMBIE, ED
通讯作者：
ABERCROMBIE, ED
影响因子：
6.9
作者：
Chen, CK;Lin, SK;Murray, RM
通讯作者：
Murray, RM