Department of Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260, USA.
Neurotox Res. 2010 Nov;18(3-4):367-76. doi: 10.1007/s12640-010-9154-6. Epub 2010 Feb 9.
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 (PPTg). When an animal is exposed to a behaviorally salient stimulus, the PPTg 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.
多巴胺系统受到多种形式的调节，反过来又对系统反应提供有效的调制。已知多巴胺神经元存在于几种活动状态。群体活动，即自发发射的多巴胺神经元的比例，受海马腹侧下托的控制。相比之下，爆发式发射被认为是多巴胺系统的行为显著输出，由脑干脚桥被盖核（PPTg）驱动。当动物暴露于行为显著的刺激时，PPTg 在多巴胺神经元中引发一连串动作电位。然而，这种爆发仅发生在自发发射的多巴胺神经元群体的一部分中。这部分由腹侧下托调节。因此，腹侧下托为行为显著的刺激提供增益或放大因子。腹侧下托本身被认为携带与环境背景相关的信息。因此，腹侧下托将根据生物体的需求和环境的特征来调整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受到干扰。在精神分裂症中，据推测，腹侧下托中间神经元调节的中断会导致多巴胺系统的过度驱动，使系统处于持续的高度警惕状态。此外，安非他命敏化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药物滥用和应激风险因素在精神病事件发生中的基础。另一方面，这可能指向腹侧下托作为治疗干预的有效部位，无论是在治疗还是甚至预防精神分裂症方面。
