Role of GABAB receptors in proepileptic and antiepileptic effects of an applied electric field in rat hippocampus in vitro

Abstract

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 GABAB 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 GABAB receptor antagonist, CGP 55845 (2 μM), could abolish applied-field induced suppression of orthodromic-stimulus evoked epileptiform afterdischarge activity in the CA1 region. GABAB 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 GABAB 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 GABAB receptor activation can serve a protective role under antiepileptic paradigms by preventing electrical stimulation from causing hyperexcitation.