Transient changes in excitability of rabbit CA3 neurons with a time course appropriate to support memory consolidation
Transient changes in excitability of rabbit CA3 neurons with a time course appropriate to support memory consolidation
复制标题
DOI：
10.1152/jn.1996.76.3.1836
复制
发表时间：
1996-09-01
影响因子：
2.5
通讯作者：
Disterhoft, JF
中科院分区：
文献类型：
--
作者：
Thompson, LT;Moyer, JR;Disterhoft, JF
1.在行为幼稚兔海马脑片中用细胞内记录评估CA 3锥体神经元的兴奋性。CA 3锥体神经元具有较大的（-13.1 +/- 0.3 mV;平均值+/- SE）爆发后超极化（AHPs），并在静息电位为-68 mV时对长时间（800 ms）去极化电流注入表现出稳健的尖峰频率适应（调节）。AHP和调节指标与来自同一切片或同一只兔子的CA 1锥体神经元的稳定记录在尺度上不同，但在种类上没有差异，CA 3神经元具有更大更长的AHP，但在放电过程中具有更少的尖峰.一组兔子接受了一项简单的联想学习任务训练，即跟踪眨眼条件反射，这需要一个完整的海马体才能成功获得。这项任务中的记忆巩固也涉及海马体，而学习反应的长期保留则没有。在201个CA 3锥体神经元中评估了学习特异性兴奋性变化的时间过程和幅度。学习增加CA 3锥体神经元的兴奋性收购后不久（1-24小时内）。平均爆发后AHP降低至未处理对照中观察到的AHP基础振幅的约一半（-6.4 +/-0.3 mV）。爆炸后AHP的面积和持续时间同样减少。在学习后不久测试的所有锥体神经元中，约有一半表现出显着降低的AHPs，而没有一个表现出增强的AHPs。在学习后1-24 h，微量条件反射也降低了CA 3区锥体神经元的调节能力。来自成功训练的兔子的神经元在响应延长的去极化时发射的动作电位（5.6 +/- 1.5）显著多于来自幼稚对照的神经元（4.1 +/- 0.2）。学习具体的住宿变化的幅度小于层次分析法。大约45%的测试神经元在学习后不久表现出明显的调节能力下降。CA 3的两种学习特异性变化都增加了神经元的兴奋性。这两种变化都具有高度的时间依赖性。AHPs在学习后1-24小时最大程度降低，然后升高，在7天内恢复到基础（初始）水平，此后保持基础水平。可容纳空间衰减到基准面的速率比AHP提前几天。其他膜特性，包括动作电位特性，静息电位，和输入电阻，是不变的学习。将观察到的变化限制在两个相互关联的兴奋性测量值上，这与早期的报告一致，即哺乳动物海马体中的学习特异性变化与有限数量的膜电导的变化有关。学习，而不是长期记忆或学习行为的表现，与兴奋性变化有关。来自兔子的神经元在经过相当长的训练后未能获得任务，没有表现出兴奋性的变化。来自伪条件化兔的神经元与行为幼稚对照的神经元难以区分。最后，来自兔子的神经元明确证明了条件反应的长期保留，与那些幼稚的对照神经元没有区别。行为变化持续了很长一段时间，但海马兴奋性的变化是短暂的，学习后不久最大。兴奋性增强了几天的时间，这段时间在其他眨眼研究中被证明是记忆巩固所必需的。由于海马的兴奋性随后恢复到基础水平，但学习任务的记忆持续存在，巩固后的记忆痕迹（“痕迹”）必须是海马外的。
1. The excitability of CA3 pyramidal neurons was assessed with intracellular recordings in hippocampal slices from behaviorally naive rabbits. CA3 pyramidal neurons had large (-13.1 +/- 0.3 mV; mean +/- SE) postburst afterhyperpolarizations (AHPs) and exhibited robust spike-frequency adaptation (accommodation) to prolonged (800-ms) depolarizing current injection at resting potentials of -68 mV. AHP and accommodation measures differed in scale but not in kind from those obtained in stable recordings from CA1 pyramidal neurons in the same slices or from the same rabbits, with CA3 neurons having larger longer AHPs but fewer spikes during accommodation.2. Groups of rabbits were trained in a simple, associative-learning task, trace eye-blink conditioning, which requires an intact hippocampus for successful acquisition. Memory consolidation in this task also involves the hippocampus, whereas long-term retention of the learned response does not. The time course and magnitude of learning-specific changes in excitability were assessed in 201 CA3 pyramidal neurons.3. Learning increased the excitability of CA3 pyramidal neurons soon after acquisition (within 1-24 h). The mean postburst AHP was reduced to approximately half (-6.4 +/- 0.3 mV) the basal amplitude of the AHP observed in naive controls. The area and duration of the postburst AHP similarly were reduced. Approximately half of all pyramidal neurons tested soon after learning exhibited significantly reduced AHPs, whereas none exhibited enhanced AHPs.4. Trace conditioning also reduced accommodation of CA3 pyramidal neurons 1-24 h after learning. Neurons from successfully trained rabbits fired significantly more action potentials (5.6 +/- 1.5) in response to prolonged depolarization than did neurons from naive controls (4.1 +/- 0.2). The magnitude of the learning-specific change in accommodation was less than that for the AHP. Approximately 45% of neurons tested exhibited significantly reduced accommodation soon after learning.5. Both learning-specific changes in CA3 increased neuronal excitability. Both changes were highly time dependent. AHPs were reduced maximally 1-24 h after learning, then increased, returning to basal (naive) levels within 7 days and remaining basal thereafter. The decay rate of accommodation to basal levels preceded that of the AHP by several days.6. Other membrane properties, including action potential characteristics, resting potential, and input resistance, were unchanged by learning. The restriction of the observed changes to two interrelated measures of excitability concurs with earlier reports that learning-specific changes in the mammalian hippocampus are linked to changes in a limited number of membrane conductances.7. Learning, not long-term memory or performance of the learned behavior, was linked to the excitability changes. Neurons from rabbits that failed to acquire the task after considerable training exhibited no excitability changes. Neurons from pseudo-conditioned rabbits were indistinguishable from neurons of behaviorally naive controls. Finally, neurons from rabbits that explicitly demonstrated long-term retention of the conditioned response were indistinguishable from those of naive controls.8. Behavioral changes persisted for extremely long periods, but the observed changes in hippocampal excitability were transient and greatest soon after learning. Excitability was enhanced for a period of a few days, a period demonstrated in other eyeblink studies to be required for memory consolidation. Because hippocampal excitability then returned to basal levels but memory of the learned task persisted, postconsolidation memory traces (the ''engram'') must be extrahippocampal.