A neurocomputational account of catalepsy sensitization induced by D2 receptor blockade in rats: context dependency, extinction, and renewal.
A neurocomputational account of catalepsy sensitization induced by D2 receptor blockade in rats: context dependency, extinction, and renewal.
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DOI：
10.1007/s00213-008-1457-4
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发表时间：
2009-06
影响因子：
3.4
通讯作者：
Frank, Michael J.
中科院分区：
文献类型：
--
作者：
Wiecki, Thomas V.;Riedinger, Katrin;von Ameln-Mayerhofer, Andreas;Schmidt, Werner J.;Frank, Michael J.
在啮齿类动物中反复氟哌啶醇治疗会导致每天的猝厥加剧（即致敏）。先前的实验表明，这种敏化是情境依赖的，并且对消失训练有抵抗力。本研究的目的是为这些发现提供一个神经生物学机制的解释。我们使用了一个基底神经节的神经计算模型，并基于多巴胺功能的奖励预测误差和新颖性假设模拟了两个备选模型。我们还进行了一个行为大鼠实验来判断这些模型之间的关系。20只雄性Sprague-Dawley大鼠连续数天服用0.25 mg/kg氟哌啶醇，随后在熟悉或新的环境中进行测试。模拟结果表明，在纹状体状神经元中，通过模拟D2受体拮抗剂的“NoGo”学习，可以解释猝死致敏及其情境依赖性，从而导致反应潜伏期越来越慢。该模型进一步显示了猝死致敏的不可熄灭成分，这是由于潜在的NoGo表征被阻止表达，因此在灭绝期间不会被遗忘。在大鼠实验中，情境依赖效应不依赖于情境的新颖性，排除了新颖性模型对情境依赖的解释。模拟提供了潜在的复杂机制，导致环境依赖的过敏性，灭绝和更新。
Repeated haloperidol treatment in rodents results in a day-to-day intensification of catalepsy (i.e., sensitization). Prior experiments suggest that this sensitization is context-dependent and resistant to extinction training. The aim of this study was to provide a neurobiological mechanistic explanation for these findings. We use a neurocomputational model of the basal ganglia and simulate two alternative models based on the reward prediction error and novelty hypotheses of dopamine function. We also conducted a behavioral rat experiment to adjudicate between these models. Twenty male Sprague–Dawley rats were challenged with 0.25 mg/kg haloperidol across multiple days and were subsequently tested in either a familiar or novel context. Simulation results show that catalepsy sensitization, and its context dependency, can be explained by “NoGo” learning via simulated D2 receptor antagonism in striatopallidal neurons, leading to increasingly slowed response latencies. The model further exhibits a nonextinguishable component of catalepsy sensitization due to latent NoGo representations that are prevented from being expressed, and therefore from being unlearned, during extinction. In the rat experiment, context dependency effects were not dependent on the novelty of the context, ruling out the novelty model's account of context dependency. Simulations lend insight into potential complex mechanisms leading to context-dependent catalepsy sensitization, extinction, and renewal.
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影响因子：
3.3
作者：
CAMPS, M;CORTES, R;PALACIOS, JM
通讯作者：
PALACIOS, JM
影响因子：
5.3
作者：
Basso, MA;Wurtz, RH
通讯作者：
Wurtz, RH
影响因子：
2
作者：
Frank, ST;Schmidt, WJ
通讯作者：
Schmidt, WJ
影响因子：
56.9
作者：
Frank, MJ;Seeberger, LC;O'Reilly, RC
通讯作者：
O'Reilly, RC
影响因子：
2.5
作者：
Bayer, Hannah M.;Lau, Brian;Glimcher, Paul W.
通讯作者：
Glimcher, Paul W.