Co-transmission of acetylcholine and GABA regulates hippocampal states.
Co-transmission of acetylcholine and GABA regulates hippocampal states.
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DOI：
10.1038/s41467-018-05136-1
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发表时间：
2018-07-20
影响因子：
16.6
通讯作者：
Nyiri G
中科院分区：
文献类型：
--
作者：
Takács VT;Cserép C;Schlingloff D;Pósfai B;Szőnyi A;Sos KE;Környei Z;Dénes Á;Gulyás AI;Freund TF;Nyiri G
人们普遍认为，基底前脑胆碱能系统通过单一神经递质的非突触传递来控制皮质功能。然而，我们发现小鼠海马胆碱能终末总是建立GABA能突触，而它们的胆碱能小泡只停靠在这些突触上。我们证明这些突触不是通过不同的小泡共同释放而是共同传递GABA和乙酰胆碱，这些小泡的释放是由不同的钙通道触发的。这种共同传递激发复合突触后电位，这些电位由突触前自身受体相互交叉调节。虽然不能研究突触后胆碱能受体的分布，但它们的反应潜伏期暗示着局灶性、突触内和/或突触周围的定位，而GABAA受体在突触内被检测到。GABA能成分单独有效地抑制海马区尖锐的波纹和癫痫样活动。因此，不同调节的GABA能和胆碱能共同传递暗示了迄今为止尚未认识到的对皮质状态的控制水平。这种新的海马胆碱能神经传递模型可能导致在神经退行性疾病中胆碱能神经失神经后的替代药物治疗。乙酰胆碱(ACh)在中枢神经系统的释放被认为是一元性的，并在容量传递中非突触地介导。在这里，Takács和他的同事展示了胆碱能终末在解剖和功能上与GABA能突触并列，GABA和ACh分子是共同传递的。
The basal forebrain cholinergic system is widely assumed to control cortical functions via non-synaptic transmission of a single neurotransmitter. Yet, we find that mouse hippocampal cholinergic terminals invariably establish GABAergic synapses, and their cholinergic vesicles dock at those synapses only. We demonstrate that these synapses do not co-release but co-transmit GABA and acetylcholine via different vesicles, whose release is triggered by distinct calcium channels. This co-transmission evokes composite postsynaptic potentials, which are mutually cross-regulated by presynaptic autoreceptors. Although postsynaptic cholinergic receptor distribution cannot be investigated, their response latencies suggest a focal, intra- and/or peri-synaptic localisation, while GABAA receptors are detected intra-synaptically. The GABAergic component alone effectively suppresses hippocampal sharp wave-ripples and epileptiform activity. Therefore, the differentially regulated GABAergic and cholinergic co-transmission suggests a hitherto unrecognised level of control over cortical states. This novel model of hippocampal cholinergic neurotransmission may lead to alternative pharmacotherapies after cholinergic deinnervation seen in neurodegenerative disorders. Acetylcholine (ACh) release in the central nervous system is thought to be unitary and mediated non-synaptically in volume transmission. Here, Takács and colleagues show cholinergic terminals juxtapose GABAergic synapses anatomically and functionally, and GABA and ACh molecules are co-transmitted.
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影响因子：
3.3
作者：
ECKENSTEIN, FP;BAUGHMAN, RW;QUINN, J
通讯作者：
QUINN, J
影响因子：
5.6
作者：
Crespel, A;Baldy-Moulinier, M;Coubes, P
通讯作者：
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影响因子：
16.2
作者：
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通讯作者：
Yakel JL
影响因子：
5.3
作者：
Bell, L. Andrew;Bell, Karen A.;McQuiston, A. Rory
通讯作者：
McQuiston, A. Rory
影响因子：
25
作者：
Girardeau, Gabrielle;Benchenane, Karim;Zugaro, Michael B.
通讯作者：
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