Clonazepam suppresses GABAB-mediated inhibition in thalamic relay neurons through effects in nucleus reticularis.
1. Experiments were carried out using patch-clamp techniques in rat thalamic slices, maintained in vitro, to examine the effects of the benzodiazepine compound, clonazepam (CZP), on intrathalamic inhibition. Bath-applied CZP reduced the gamma-aminobutyric acid-B (GABAB) component of inhibitory postsynaptic potentials and currents (IPSPs and IPSCs, respectively) evoked in rat thalamic somatosensory relay neurons by stimulation of nucleus reticularis thalami (nRt), without consistently affecting the GABAA IPSP. Secondary IPSPs, which occur as a result of intrathalamic oscillations, were dramatically reduced. 2. Voltage-clamp experiments combined with local or bath perfusion of the GABAA antagonist bicuculline methiodide (BMI), demonstrated that nRt is a site of GABAA-mediated postsynaptic inhibition that affects inhibitory output onto relay neurons. BMI enhanced both GABAA and GABAB postsynaptic inhibition in relay neurons when applied to nRt. Focal applications in the ventrobasal relay nucleus near the recording electrode blocked the GABAA-mediated IPSP but had no effects on GABAB inhibitory potentials. 3. Results suggest that CZP acts to facilitate recurrent inhibition in nRt and decrease its inhibitory output onto relay neurons. Intra-nRt GABAA-mediated inhibition thus has an important role in controlling thalamic excitability and in the anti-absence actions of CZP.
Huguenard
J R
JR
Department of Neurology and Neurological Sciences, Stanford University Medical Center, California 94305.
Prince
D A
DA
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology*; D046508:Culture Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects; D051381:Rats; D018080:Receptors, GABA-B / Q000187:drug effects*; D013003:Somatosensory Cortex / Q000187:drug effects; D013787:Thalamic Nuclei / Q000187:drug effects*
D018080:Receptors, GABA-B; D002998:Clonazepam; D001640:Bicuculline