Disruption of circadian timing increases synaptic inhibition and reduces cholinergic responsiveness in the dentate gyrus.
Disruption of circadian timing increases synaptic inhibition and reduces cholinergic responsiveness in the dentate gyrus.
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DOI：
10.1002/hipo.23301
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发表时间：
2021-04
期刊：
影响因子：
3.5
通讯作者：
Ruby NF
中科院分区：
文献类型：
--
作者：
McMartin L;Kiraly M;Heller HC;Madison DV;Ruby NF
我们研究了海马体中的突触机制，这些机制可以解释昼夜节律时间的丧失如何导致空间和识别记忆的损伤。实验是在西伯利亚仓鼠（Phodopus sungorus）的海马切片中进行的，因为与小鼠和大鼠不同，它们的昼夜节律很容易消除，而不需要修改它们的基因组，也不需要手术操作，从而使神经元回路保持完整。CA 1区和齿状回颗粒细胞中兴奋性突触后场电位和群体尖峰的记录显示，昼夜节律性心律失常对突触回路的基本功能（包括长时程增强）没有影响。然而，昼夜节律紊乱动物的齿状颗粒细胞比昼夜节律完整动物的细胞保持更多的去极化静息膜电位;这些细胞中有显著更大比例的细胞对胆碱能激动剂卡巴胆碱（10 μM）作出反应而去极化，并且通过将其膜电位增加到对照（夹带）组细胞的3倍来实现。齿状回颗粒细胞从癫痫动物也表现出较高水平的紧张性抑制，测量自发抑制性突触后电位的频率。卡巴胆碱还降低了来自完整和癫痫动物的齿状颗粒细胞中刺激诱发的突触兴奋，但仅降低了来自对照仓鼠的细胞中刺激诱发的突触抑制。这些研究结果表明，昼夜节律定时的损失伴随着更大的紧张性抑制，并增加突触抑制响应于齿状颗粒细胞中的毒蕈碱受体激活。增加抑制可能会减弱齿状-CA 3微回路中的兴奋，这反过来可能解释先前在昼夜节律仓鼠中观察到的空间记忆缺陷。
We investigated synaptic mechanisms in the hippocampus that could explain how loss of circadian timing leads to impairments in spatial and recognition memory. Experiments were performed in hippocampal slices from Siberian hamsters (Phodopus sungorus) because, unlike mice and rats, their circadian rhythms are easily eliminated without modifications to their genome and without surgical manipulations, thereby leaving neuronal circuits intact. Recordings of excitatory postsynaptic field potentials and population spikes in area CA1 and dentate gyrus granule cells revealed no effect of circadian arrhythmia on basic functions of synaptic circuitry, including long‐term potentiation. However, dentate granule cells from circadian‐arrhythmic animals maintained a more depolarized resting membrane potential than cells from circadian‐intact animals; a significantly greater proportion of these cells depolarized in response to the cholinergic agonist carbachol (10 μM), and did so by increasing their membrane potential three‐fold greater than cells from the control (entrained) group. Dentate granule cells from arrhythmic animals also exhibited higher levels of tonic inhibition, as measured by the frequency of spontaneous inhibitory postsynaptic potentials. Carbachol also decreased stimulus‐evoked synaptic excitation in dentate granule cells from both intact and arrhythmic animals as expected, but reduced stimulus‐evoked synaptic inhibition only in cells from control hamsters. These findings show that loss of circadian timing is accompanied by greater tonic inhibition, and increased synaptic inhibition in response to muscarinic receptor activation in dentate granule cells. Increased inhibition would likely attenuate excitation in dentate‐CA3 microcircuits, which in turn might explain the spatial memory deficits previously observed in circadian‐arrhythmic hamsters.
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影响因子：
16.2
作者：
DOZE, VA;COHEN, GA;MADISON, DV
通讯作者：
MADISON, DV
影响因子：
5.5
作者：
COLE, AE;NICOLL, RA
通讯作者：
NICOLL, RA
影响因子：
3.5
作者：
Dannenberg H;Young K;Hasselmo M
通讯作者：
Hasselmo M
影响因子：
2.7
作者：
Kremin, T;Gerber, D;Hasselmo, ME
通讯作者：
Hasselmo, ME
DOI：
10.1101/lm.038877.115
发表时间：
2015-09
期刊：
Learning & memory (Cold Spring Harbor, N.Y.)
影响因子：
--
作者：
Krishnan HC;Lyons LC
通讯作者：
Lyons LC