Topic: GABAB

Seizure control by electrical stimulation: parameters and mechanisms

Seizure suppression by deep brain stimulation (DBS) applies high frequency stimulation (HFS) to grey matter to block seizures. In this presentation, I will present the results of a different method that employs low frequency stimulation (LFS) (1 to 10Hz) of white matter tracts to prevent seizures. The approach has been shown to be effective in the hippocampus by stimulating the ventral and dorsal hippocampal commissure in both animal and human studies respectively for mesial temporal lobe seizures. A similar stimulation paradigm has been shown to be effective at controlling focal cortical seizures in rats with corpus callosum stimulation. This stimulation targets the axons of the corpus callosum innervating the focal zone at low frequencies (5 to 10Hz) and has been shown to significantly reduce both seizure and spike frequency. The mechanisms of this suppression paradigm have been elucidated with in-vitro studies and involve the activation of two long-lasting inhibitory potentials GABAB and sAHP. LFS mechanisms are similar in both hippocampus and cortical brain slices. Additionally, the results show that LFS does not block seizures but rather decreases the excitability of the tissue to prevent seizures. Three methods of seizure suppression, LFS applied to fiber tracts, HFS applied to focal zone and stimulation of the anterior nucleus of the thalamus (ANT) were compared directly in the same animal in an in-vivo epilepsy model. The results indicate that LFS generated a significantly higher level of suppression, indicating LFS of white matter tract could be a useful addition as a stimulation paradigm for the treatment of epilepsy.

Characterization of de novo GABAB2 variants linked to Rett Syndrome and Encephalopathic Epilepsy

Functional characterization of monoallelic de novo GABAB receptor variants identified in neurological and psychiatric disorders

GABAB Receptor-mediated effects in VIP-Expressing Interneurons of the Dentate Gyrus

Induction of phasic neurotransmitter release via presynaptic GABAB receptors on medial habenula terminals

Pathogenic effects of GABAB receptor antibodies from patients with autoimmune encephalitis on neuronal signaling and network excitability

Pathogenic effects of GABAB receptor antibodies from patients with autoimmune encephalitis on synaptic structure and memory

Postsynaptic GABAB receptors inhibit synaptic plasticity at Mossy fibre input onto the basket cells of the Dentate Gyrus

Synaptotagmin-11 controls GABAB receptor internalization