Inhibitory or excitatory? Optogenetic interrogation of the functional roles of GABAergic interneurons in epileptogenesis

Journal of Biomedical Science

Review

Hui Ye¹  Stephanie Kaszuba¹ 

[1] Department of Biology, Loyola University Chicago, Quinlan Life Sciences Education and Research Center, 1032 W. Sheridan Rd, 60660, Chicago, IL, USA;

关键词: Epilepsy;    GABAergic interneurons;    Optogenetics;   

DOI  :  10.1186/s12929-017-0399-8

 received in 2017-09-20, accepted in 2017-11-28,  发布年份 2017

来源: Springer

【 摘 要 】

Alteration in the excitatory/inhibitory neuronal balance is believed to be the underlying mechanism of epileptogenesis. Based on this theory, GABAergic interneurons are regarded as the primary inhibitory neurons, whose failure of action permits hyperactivity in the epileptic circuitry. As a consequence, optogenetic excitation of GABAergic interneurons is widely used for seizure suppression. However, recent evidence argues for the context-dependent, possibly “excitatory” roles that GABAergic cells play in epileptic circuitry. We reviewed current optogenetic approaches that target the “inhibitory” roles of GABAergic interneurons for seizure control. We also reviewed interesting evidence that supports the “excitatory” roles of GABAergic interneurons in epileptogenesis. GABAergic interneurons can provide excitatory effects to the epileptic circuits via several distinct neurological mechanisms. (1) GABAergic interneurons can excite postsynaptic neurons, due to the raised reversal potential of GABA receptors in the postsynaptic cells. (2) Continuous activity in GABAergic interneurons could lead to transient GABA depletion, which prevents their inhibitory effect on pyramidal cells. (3) GABAergic interneurons can synchronize network activity during seizure. (4) Some GABAergic interneurons inhibit other interneurons, causing disinhibition of pyramidal neurons and network hyperexcitability. The dynamic, context-dependent role that GABAergic interneurons play in seizure requires further investigation of their functions at single cell and circuitry level. New optogenetic protocols that target GABAergic inhibition should be explored for seizure suppression.

【 授权许可】

CC BY   
© The Author(s). 2017