GABAB receptor-mediated responses in GABAergic projection neurones of rat nucleus reticularis thalami in vitro.
1. Whole-cell voltage-clamp recordings were obtained from GABAergic neurones of rat nucleus reticularis thalami (NRT) in vitro to assess pre- and postsynaptic GABAB receptor-mediated responses. Presynaptic inhibition of GABA release was studied at terminals on local axon collaterals within NRT as well as on projection fibres in the somatosensory relay nuclei. 2. The GABAB receptor agonist (R)-baclofen (10 microM) reduced monosynaptically evoked GABAA-mediated inhibitory postsynaptic currents (IPSCs) in NRT and somatosensory relay cells to 11 and 12% of control, respectively. 3. Action potential-independent miniature IPSCs (mIPSCs) were observed in both cell types. Mean mIPSC amplitude was 20 pA in both NRT and relay cells at a holding potential of 0 mV. The mean mIPSC frequencies were 0.83 and 2.2 Hz in NRT and relay cells, respectively. Baclofen decreased mIPSP frequency by about half in each cell type without affecting amplitude. 4. Paired-burst inhibition of evoked IPSCs was studied in relay and NRT cells by applying pairs of 100 Hz stimulus bursts separated by 600 ms. The mean ratio of second to first peak IPSC amplitudes was 0.77. 5. In NRT cells baclofen induced a linear postsynaptic conductance increase of 0.82 nS with an associated reversal potential of -121 mV. A small (0.14 nS) GABAB component of the evoked IPSC was detected in only a minority of NRT cells (3 of 18). 6. All pre- and postsynaptic effects of baclofen, as well as PBI, were largely reversed by the specific GABAB receptor antagonist CGP 35348 (0.5 mM). 7. We conclude that activation of GABAB receptors in NRT leads to presynaptic autoinhibition of IPSCs in both NRT and relay cells, and to direct activation of a small linear K+ conductance. In addition our experiments suggest that reciprocal connectivity within NRT can be partially mediated by a small GABAB inhibitory event.
Ulrich
D
D
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305, USA. Ulrich@leland.stanford.edu
Huguenard
J R
JR
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004594:Electrophysiology; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology; D013787:Thalamic Nuclei / Q000166:cytology / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D015221:Potassium Channels; D018080:Receptors, GABA-B; D017661:Receptors, Presynaptic; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D001418:Baclofen