Optogenetic release of ACh induces rhythmic bursts of perisomatic IPSCs in hippocampus.
Optogenetic release of ACh induces rhythmic bursts of perisomatic IPSCs in hippocampus.
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DOI：
10.1371/journal.pone.0027691
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Alger BE
中科院分区：
文献类型：
--
作者：
Nagode DA;Tang AH;Karson MA;Klugmann M;Alger BE
乙酰胆碱(ACh)影响大脑皮层系统的一系列现象。它改变了许多离子电导和神经元的放电行为，通常是通过调节细胞群体中的膜电位振荡来实现的。突触抑制在许多形式的振荡中起着至关重要的作用，胆碱能机制既调节振荡又调节突触抑制。使用胆碱能受体激动剂或全身组织电刺激释放内源性ACh的体外研究，已经导致了对胆碱能功能的深入了解，但由于这些形式的刺激相对缺乏选择性，问题仍然存在。为了研究ACh选择性释放对中间神经元和振荡的影响，我们采用光遗传学的方法，在胆碱-乙酰转移酶(ChAT)启动子的控制下，将光敏的非选择性阳离子通道Channelopoursin2(ChR2)病毒输送到表达Cre重组酶的成年小鼠Broca内侧隔/斜角带(MS/DBB)的胆碱能投射神经元。从这些动物获得的急性海马片在几周后发现ChR2在胆碱能轴突中表达。在未经处理的脑片上，短时间的蓝光脉冲在CA1区锥体细胞上引起ACh诱发的抑制性突触后电流(L-IPSCs)的爆发，在光刺激停止后持续10‘S秒。L-IPSC发生在用eserine和非常低浓度的4-AP处理的切片中更可靠，因此在大多数实验中都使用了这种方法。节律性L-IPSCs主要由M受体驱动，并可被锥体细胞释放的内源性大麻素所抑制。最后，局域场电位的低频振荡(LFO)与L-IPSCs显著相关，锥体附近LFO的逆转证实了LFP是由周身抑制驱动的。这种光遗传学方法可能是未来研究内源性ACh效应的一种有用的补充技术。
Acetylcholine (ACh) influences a vast array of phenomena in cortical systems. It alters many ionic conductances and neuronal firing behavior, often by regulating membrane potential oscillations in populations of cells. Synaptic inhibition has crucial roles in many forms of oscillation, and cholinergic mechanisms regulate both oscillations and synaptic inhibition. In vitro investigations using bath-application of cholinergic receptor agonists, or bulk tissue electrical stimulation to release endogenous ACh, have led to insights into cholinergic function, but questions remain because of the relative lack of selectivity of these forms of stimulation. To investigate the effects of selective release of ACh on interneurons and oscillations, we used an optogenetic approach in which the light-sensitive non-selective cation channel, Channelrhodopsin2 (ChR2), was virally delivered to cholinergic projection neurons in the medial septum/diagonal band of Broca (MS/DBB) of adult mice expressing Cre-recombinase under the control of the choline-acetyltransferase (ChAT) promoter. Acute hippocampal slices obtained from these animals weeks later revealed ChR2 expression in cholinergic axons. Brief trains of blue light pulses delivered to untreated slices initiated bursts of ACh-evoked, inhibitory post-synaptic currents (L-IPSCs) in CA1 pyramidal cells that lasted for 10's of seconds after the light stimulation ceased. L-IPSC occurred more reliably in slices treated with eserine and a very low concentration of 4-AP, which were therefore used in most experiments. The rhythmic, L-IPSCs were driven primarily by muscarinic ACh receptors (mAChRs), and could be suppressed by endocannabinoid release from pyramidal cells. Finally, low-frequency oscillations (LFOs) of local field potentials (LFPs) were significantly cross-correlated with the L-IPSCs, and reversal of the LFPs near s. pyramidale confirmed that the LFPs were driven by perisomatic inhibition. This optogenetic approach may be a useful complementary technique in future investigations of endogenous ACh effects.
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影响因子：
5.5
作者：
Cobb, SR;Davies, CH
通讯作者：
Davies, CH
单个海马GABA能突触的突触后反应的释放概率依赖性尺度。
DOI：
10.1523/jneurosci.3106-06.2006
发表时间：
2006-11-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Biró AA;Holderith NB;Nusser Z
通讯作者：
Nusser Z
影响因子：
64.8
作者：
COBB, SR;BUHL, EH;SOMOGYI, P
通讯作者：
SOMOGYI, P
影响因子：
16.2
作者：
Gu Z;Yakel JL
通讯作者：
Yakel JL
影响因子：
4.7
作者：
Karson, Miranda A.;Whittington, Kevin C.;Alger, Bradley E.
通讯作者：
Alger, Bradley E.