Meeter M, Murre J M J, Talamini L M
Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.
Hippocampus. 2004;14(6):722-41. doi: 10.1002/hipo.10214.
It has been suggested that hippocampal mode shifting between a storage and a retrieval state might be under the control of acetylcholine (ACh) levels, as set by an autoregulatory hippocampo-septo-hippocampal loop. The present study investigates how such a mechanism might operate in a large-scale connectionist model of this circuitry that takes into account the major hippocampal subdivisions, oscillatory population dynamics and the time scale on which ACh exerts its effects in the hippocampus. The model assumes that hippocampal mode shifting is regulated by a novelty signal generated in the hippocampus. The simulations suggest that this signal originates in the dentate. Novel patterns presented to this structure lead to brief periods of depressed firing in the hippocampal circuitry. During these periods, an inhibitory influence of the hippocampus on the septum is lifted, leading to increased firing of cholinergic neurons. The resulting increase in ACh release in the hippocampus produces network dynamics that favor learning over retrieval. Resumption of activity in the hippocampus leads to the reinstatement of inhibition. Despite theta-locked rhythmic firing of ACh neurons in the septum, ACh modulation in the model fluctuates smoothly on a time scale of seconds. It is shown that this is compatible with the time scale on which memory processes take place. A number of strong predictions regarding memory function are derived from the model.
有人提出，海马体在存储和检索状态之间的模式转换可能受乙酰胆碱（ACh）水平的控制，而这一水平由海马体-隔区-海马体自动调节回路设定。本研究探讨了这种机制在该神经回路的大规模连接主义模型中是如何运作的，该模型考虑了海马体的主要亚区、振荡群体动力学以及ACh在海马体中发挥作用的时间尺度。该模型假设海马体模式转换受海马体中产生的新奇信号调节。模拟结果表明，该信号起源于齿状回。呈现给该结构的新异模式会导致海马体神经回路出现短暂的放电抑制期。在这些时期，海马体对隔区的抑制作用解除，导致胆碱能神经元放电增加。海马体中由此产生的ACh释放增加会产生有利于学习而非检索的网络动力学。海马体恢复活动会导致抑制作用的恢复。尽管隔区中的ACh神经元有θ节律锁定的节律性放电，但模型中的ACh调制在数秒的时间尺度上平稳波动。结果表明，这与记忆过程发生的时间尺度是相符的。该模型得出了一些关于记忆功能的有力预测。
