Regulating hippocampal hyperexcitability through GABAB Receptors
Min Lang1, Homeira Moradi-Chameh, Tariq Zahid
1Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
Physiological Reports
|April 29, 2014
Summary
GABAergic inhibition disruptions cause epilepsy. This study shows GABAB receptor modulation impacts hippocampal hyperexcitability, suggesting potential therapeutic strategies for seizure control.
Area of Science:
- Neuroscience
- Epileptology
- Pharmacology
Background:
- Disturbances in GABAergic inhibition are a primary cause of epileptic seizures.
- While GABAA receptor malfunction is known, the role of GABAB receptors in seizure activity remains unclear.
Purpose of the Study:
- To investigate the anticonvulsive effects of GABAB receptors in a mouse model of hippocampal kindling and slices.
- To explore the potential of GABAB receptor positive allosteric modulators in managing seizure-related hyperexcitability.
Main Methods:
- Utilized a mouse model of hippocampal kindling and ex vivo hippocampal slices.
- Administered GS 39783 (GABAB positive allosteric modulator) and CGP 55845 (GABAB antagonist).
- Recorded hippocampal EEG, aberrant spikes, excitatory field potentials, and CA3 pyramidal neuron activity.
Main Results:
- GS 39783 reduced aberrant hippocampal spikes but did not attenuate EEG discharges.
- CGP 55845 prolonged discharges, increased spike incidence, and facilitated excitatory field potentials.
- GS 39783 and baclofen (GABAB agonist) together abolished excitatory field potentials, indicating GABAB receptor involvement.
Conclusions:
- GABAB receptors regulate hippocampal hyperexcitability by inhibiting CA3 glutamatergic synapses.
- Positive allosteric modulation of GABAB receptors shows promise for reducing seizure-related hyperexcitability.
- Targeting GABAB receptors may offer novel therapeutic avenues for epilepsy treatment.
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