Enhancement of Asynchronous Release from Fast-Spiking Interneuron in Human and Rat Epileptic Neocortex

Jiang, Man; Zhu, Jie; Liu, Yaping; Yang, Mingpo; Tian, Cuiping; Jiang, Shan; Wang, Yonghong; Guo, Hui; Wang, Kaiyan; Shu, Yousheng

doi:10.1371/journal.pbio.1001324

Cited by 80 publications

(82 citation statements)

References 63 publications

(81 reference statements)

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“…In the present study, we demonstrated that SynII deletion reduced IPSC amplitudes and prolonged the release kinetics in PV interneurons, which have a key role in the regulation of seizure propagation (Krook-Magnuson et al, 2013;Sessolo et al, 2015). Furthermore, extensive evidence links epilepsy with asynchronous activity of GABAergic synapses through tonic inhibition (Jiang et al, 2012;Pandit et al, 2013;Medrihan et al, 2015). We demonstrated here that SynII maintains the asynchronous release component at CCK interneurons, which are thought to contribute to vulnerability of neuronal networks to seizure activity (Wyeth et al, 2010;Lee and Soltesz, 2011).…”

Section: Discussionmentioning

confidence: 99%

Synapsin II Regulation of GABAergic Synaptic Transmission Is Dependent on Interneuron Subtype

et al. 2017

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Synapsins are epilepsy susceptibility genes that encode phosphoproteins reversibly associated with synaptic vesicles. Synapsin II (SynII) gene deletion produces a deficit in inhibitory synaptic transmission, and this defect is thought to cause epileptic activity. We systematically investigated how SynII affects synchronous and asynchronous release components of inhibitory transmission in the CA1 region of the mouse hippocampus. We found that the asynchronous GABAergic release component is diminished in SynII-deleted (SynII(Ϫ)) slices. To investigate this defect at different interneuron subtypes, we selectively blocked either N-type or P/Q-type Ca 2ϩ channels. SynII deletion suppressed the asynchronous release component at synapses dependent on N-type Ca 2ϩ channels but not at synapses dependent on P/Q-type Ca 2ϩ channels. We then performed paired double-patch recordings from inhibitory basket interneurons connected to pyramidal neurons and used cluster analysis to classify interneurons according to their spiking and synaptic parameters. We identified two cell subtypes, presumably parvalbumin (PV) and cholecystokinin (CCK) expressing basket interneurons. To validate our interneuron classification, we took advantage of transgenic animals with fluorescently labeled PV interneurons and confirmed that their spiking and synaptic parameters matched the parameters of presumed PV cells identified by the cluster analysis. The analysis of the release time course at the two interneuron subtypes demonstrated that the asynchronous release component was selectively reduced at SynII(Ϫ) CCK interneurons. In contrast, the transmission was desynchronized at SynII(Ϫ) PV interneurons. Together, our results demonstrate that SynII regulates the time course of GABAergic release, and that this SynII function is dependent on the interneuron subtype.

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Section: Discussionmentioning

confidence: 99%

Synapsin II Regulation of GABAergic Synaptic Transmission Is Dependent on Interneuron Subtype

et al. 2017

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“…In some hippocampal interneurons, asynchronous vesicle fusion is the predominant form of neurotransmitter release (Lu and Trussell, 2000;Hefft and Jonas, 2005;Ali and Todorova, 2010;Daw et al, 2010). In cortical interneurons, asynchronous release may play an important role in regulating epileptoform activity (Manseau et al, 2010;Jiang et al, 2012;Medrihan et al, 2015). In excitatory synapses, asynchronous release can generate larger and prolonged postsynaptic responses and perhaps play a role in potentiation and plasticity (Iremonger and Bains, 2007;Peters et al, 2010;Rudolph et al, 2011).…”

Section: An Overview Of the Synaptic Vesicle Cyclementioning

confidence: 99%

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

Kavalali

2017

Pharmacol Rev

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“…2A). GABAergic dysfunction in epilepsy may result in subtle alterations in inhibitory circuits [23,24] , and the down-regulation of GABAergic inhibition may cause epileptiform activity [25] . In ka inic acid (KA)-lesioned rats, the amplitude and conductance of both non-NMDA and NMDA components of excitatory postsynaptic currents (EPSCs) are signifi cantly reduced in stratum lacunosum-moleculare interneurons, but the rise-time of EPSCs is not signifi cantly changed [26] .…”

Section: Interneuron Fate and Functional Cor Relates In Epilepsymentioning

confidence: 99%

Dysfunction of hippocampal interneurons in epilepsy

Liu

et al. 2014

Neurosci. Bull.

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Gamma-amino-butyric acid (GABA)-containing interneurons are crucial to both development and function of the brain. Down-regulation of GABAergic inhibition may result in the generation of epileptiform activity. Loss, axonal sprouting, and dysfunction of interneurons are regarded as mechanisms involved in epileptogenesis. Recent evidence suggests that network connectivity and the properties of interneurons are responsible for excitatory-inhibitory neuronal circuits. The balance between excitation and inhibition in CA1 neuronal circuitry is considerably altered during epileptic changes. This review discusses interneuron diversity, the causes of interneuron dysfunction in epilepsy, and the possibility of using GABAergic neuronal progenitors for the treatment of epilepsy.

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Enhancement of Asynchronous Release from Fast-Spiking Interneuron in Human and Rat Epileptic Neocortex

Abstract: Asynchronous GABA release occurs at output synapses of fast-spiking interneurons in human and rat neocortex and is elevated in epileptic tissues from both species.

Cited by 80 publications

References 63 publications

Synapsin II Regulation of GABAergic Synaptic Transmission Is Dependent on Interneuron Subtype

Synapsin II Regulation of GABAergic Synaptic Transmission Is Dependent on Interneuron Subtype

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

Dysfunction of hippocampal interneurons in epilepsy

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