Evidence for encoding versus retrieval scheduling in the hippocampus by theta phase and acetylcholine.
Evidence for encoding versus retrieval scheduling in the hippocampus by theta phase and acetylcholine.
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DOI：
10.1523/jneurosci.4483-12.2013
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发表时间：
2013-05-15
期刊：
影响因子：
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通讯作者：
Lever C
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文献类型：
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作者：
Douchamps V;Jeewajee A;Blundell P;Burgess N;Lever C
新记忆的形成需要在面对过去的主动干扰时对新信息进行编码。对于海马区CA1，提出了两种解决方案：1)在新事物中释放的乙酰胆碱选择性地抑制CA3对CA1的兴奋性投射（介导检索产物），同时保留内嗅输入（介导新的感觉信息）；2)编码优先发生在锥体层θ峰，与内嗅皮层输入一致，检索优先发生在谷，与CA3输入一致，符合theta相位依赖性突触可塑性。我们检验了这些模型的三个预测：1)在新的环境中，CA1位置细胞放电的首选θ波相位应该更靠近CA1锥体层θ波峰值，将编码-检索平衡转向编码；2)新环境下编码相关的转变可能会被胆碱能拮抗所破坏；3)在熟悉的环境中，胆碱能拮抗作用会使首选θ波发射阶段更靠近θ波波谷，使编码-检索平衡进一步向检索方向移动。我们通过记录自由移动的大鼠在开阔的野外环境中在东莨菪碱（一种健健性胆碱能拮抗剂）或载体（生理盐水）的影响下觅食的CA1锥体细胞来测试这些预测。结果证实了这三个预测，支持theta相位和编码-检索动力学的胆碱能模型。与胆碱能增强编码一致，东莨菪碱减弱了新环境中不同空间表征的形成，降低了位置细胞“重新映射”的程度。
The formation of new memories requires new information to be encoded in the face of proactive interference from the past. Two solutions have been proposed for hippocampal region CA1: 1) acetylcholine, released in novelty, selectively suppresses excitatory projections to CA1 from CA3 (mediating the products of retrieval), while sparing entorhinal inputs (mediating novel sensory information); 2) encoding preferentially occurs at the pyramidal-layer theta peak, coincident with input from entorhinal cortex, and retrieval occurs at the trough, coincident with input from CA3, consistent with theta-phase-dependent synaptic plasticity. We examined three predictions of these models: 1) In novel environments, the preferred theta phase of CA1 place cell firing should shift closer to the CA1 pyramidal-layer theta peak, shifting the encoding-retrieval balance towards encoding; 2) The encoding-related shift in novel environments should be disrupted by cholinergic antagonism; 3) In familiar environments, cholinergic antagonism should shift the preferred theta firing phase closer to the theta trough, shifting the encoding-retrieval balance even further towards retrieval. We tested these predictions by recording from CA1 pyramidal cells in freely moving rats as they foraged in open field environments under the influence of scopolamine (an amnestic cholinergic antagonist) or vehicle (saline). Results confirmed all three predictions, supporting both the theta phase and cholinergic models of encoding-vs-retrieval dynamics. Also consistent with cholinergic enhancement of encoding, scopolamine attenuated the formation of distinct spatial representations in a new environment, reducing the extent of place cell “remapping”.