Moxon Karen A, Gerhardt Greg A, Gulinello Maria, Adler Lawrence E
Drexel University, School of Biomedical Engineering, Science and Health Systems, Philadelphia, PA 19104, USA.
Biol Cybern. 2003 Apr;88(4):247-64. doi: 10.1007/s00422-002-0373-7.
A model of the CA3 region of the hippocampus was used to simulate the P50 auditory-evoked potential response to repeated stimuli in order to study the neuronal circuits involved in a sensory-processing deficit associated with schizophrenia. Normal subjects have a reduced P50 auditory-evoked potential amplitude in response to the second of two paired auditory click stimuli spaced 0.5 s apart. However, schizophrenic patients do not gate or reduce their response to the second click. They have equal auditory-evoked response amplitudes to both clicks. When schizophrenic patients were medicated with traditional neuroleptics, the evoked potential amplitude to both clicks increased, but gating of the second response was not restored or improved. Animal studies suggest a role for septohippocampal cholinergic activity in sensory gating. We used a computational model of this system in order to study the relative contributions of local processing and afferent activity in sensory gating. We first compared the effect of information representation as average firing rate to information representation as cell assemblies in order to evaluate the best method to represent the response of hippocampal neurons to the auditory click. We then studied the effects of nicotinic cholinergic input on the response of the network and the effect of GABA(B) receptor activation on the ability of the local network to suppress the test response. The results of our model showed that nicotinic cholinergic input from the septum to the hippocampus can control the flow of sensory information from the cortex into the hippocampus. In addition, postsynaptic GABA(B) receptor activation was not sufficient to suppress the test response when the interstimulus interval was 500 ms. However, presynaptic GABA(B) receptor activity may be responsible for the suppression of the test response at this interstimulus interval.
为了研究与精神分裂症相关的感觉处理缺陷所涉及的神经回路，我们使用海马体CA3区域的模型来模拟对重复刺激的P50听觉诱发电位反应。正常受试者在对间隔0.5秒的两个配对听觉点击刺激中的第二个刺激做出反应时，P50听觉诱发电位幅度会降低。然而，精神分裂症患者不会对第二个点击进行门控或降低反应。他们对两个点击的听觉诱发电位幅度相等。当精神分裂症患者使用传统抗精神病药物治疗时，对两个点击的诱发电位幅度都会增加，但第二个反应的门控并未恢复或改善。动物研究表明，隔海马胆碱能活动在感觉门控中起作用。我们使用该系统的计算模型来研究局部处理和传入活动在感觉门控中的相对贡献。我们首先比较了以平均放电率表示信息与以细胞集合表示信息的效果，以评估表示海马神经元对听觉点击反应的最佳方法。然后，我们研究了烟碱型胆碱能输入对网络反应的影响以及GABA(B)受体激活对局部网络抑制测试反应能力的影响。我们模型的结果表明，从隔区到海马体的烟碱型胆碱能输入可以控制感觉信息从皮质流入海马体。此外，当刺激间隔为500毫秒时，突触后GABA(B)受体激活不足以抑制测试反应。然而，突触前GABA(B)受体活动可能是在这个刺激间隔下抑制测试反应的原因。
