Ghoshal Ayan, Conn P Jeffrey
Vanderbilt Center for Neuroscience Drug Discovery, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA.
Future Neurol. 2015;10(2):115-128. doi: 10.2217/FNL.14.63.
The hippocampo-prefrontal (H-PFC) pathway has been linked to cognitive and emotional disturbances in several psychiatric disorders including schizophrenia. Preclinical evidence from the NMDA receptor antagonism rodent model of schizophrenia shows severe pathology selective to the H-PFC pathway. It is speculated that there is an increased excitatory drive from the hippocampus to the prefrontal cortex due to dysfunctions in the H-PFC plasticity, which may serve as the basis for the behavioral consequences observed in this rodent model. Thus, the H-PFC pathway is currently emerging as a promising therapeutic target for the negative and cognitive symptom clusters of schizophrenia. Here, we have reviewed the physiological, pharmacological and functional characteristics of the H-PFC pathway and we propose that allosteric activation of glutamatergic and cholinergic neurotransmission can serve as a plausible therapeutic approach.
海马体-前额叶皮质（H-PFC）通路与包括精神分裂症在内的多种精神疾病中的认知和情绪障碍有关。来自精神分裂症NMDA受体拮抗啮齿动物模型的临床前证据表明，H-PFC通路存在严重的选择性病理变化。据推测，由于H-PFC可塑性功能障碍，海马体对前额叶皮质的兴奋性驱动增加，这可能是该啮齿动物模型中观察到的行为后果的基础。因此，H-PFC通路目前正成为治疗精神分裂症阴性和认知症状群的一个有前景的治疗靶点。在此，我们综述了H-PFC通路的生理、药理和功能特性，并提出谷氨酸能和胆碱能神经传递的变构激活可作为一种合理的治疗方法。
