Role of GABAB receptors in proepileptic and antiepileptic effects of an applied electrical field in rat hippocampus in vitro - Forskning

DOI

https://doi.org/10.1016/j.brainres.2018.12.043
Forlagets udgivne version

The mechanisms underlying antiepileptic effects of deep brain stimulation (DBS) are complex and poorly understood. Studies on the effects of applied electric fields on epileptic nervous tissue could enable future advances in DBS treatments. Applied electric fields are known to inhibit or enhance epileptic activity in vitro through direct effects on local neurons, but it is unclear whether trans-synaptic effects participate in such actions. The present study investigates, in an epileptic brain slice model, the influence of GABA _B receptor activation on excitatory and suppressive effects of a short-duration (10 ms) electric field in rat hippocampus. The results show that perfusion of the GABA _B receptor antagonist, CGP 55845 (2 μM), could abolish applied-field induced suppression of orthodromic-stimulus evoked epileptiform afterdischarge activity in the CA1 region. GABA _B receptor blockade was associated with an enhanced excitatory (proepileptic) effect of the applied field. However, the suppressive effect, observed in isolation using weak field stimuli, was left unchanged. The G-protein-activated inwardly rectifying K ⁺ channel (GIRK) antagonist, tertiapin (30–50 nM), mimicked the effects of CGP 55845. The results suggest that the applied field activate (elements of) local interneurons to release GABA onto GABA _B receptors. The resulting activation of postsynaptic GIRK channels inhibits neuronal activity thereby dampening the direct stimulatory effect of the applied field. The study indicates that local-stimulus induced GABA _B receptor activation can serve a protective role under antiepileptic paradigms by preventing electrical stimulation from causing hyperexcitation.

Originalsprog	Engelsk
Tidsskrift	Brain Research
Vol/bind	1710
Nummer	May
Sider (fra-til)	157-162
Antal sider	6
ISSN	0006-8993
DOI	https://doi.org/10.1016/j.brainres.2018.12.043
Status	Udgivet - 2019

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Role of GABA_B receptors in proepileptic and antiepileptic effects of an applied electrical field in rat hippocampus in vitro

DOI