Glycine receptors contribute to synaptic inhibition in rat ventrobasal thalamus

Ahmad A. Ghavanini *, David A. Mathers †, and Ernie Puil ‡. (Introducing Member: Dr. Michael J.A. Walker). *Program in Neuroscience, †Department of Physiology, and ‡Department of Pharmacology & Therapeutics and Department of Anesthesia, The University of British Columbia, Vancouver, B.C, Canada.

γ-aminobutyrate (GABA) has a well-established role in synaptic inhibition of thalamus (Kim et al. 1997). Whereas GABA and glycine are often co-transmitters (Dumoulin et al. 2001), a contribution of glycine receptors to synaptic inhibition of thalamus has not received extensive investigation.

We examined the possibility that functional glycine receptors exist in dorsal thalamus and whether they contribute to synaptic inhibition in thalamocortical neurons.

Parasagittal brain slices of 13-15 day-old Sprague-Dawley rats (either sex) were investigated. Slices were examined with multiphoton confocal microscopy for the presence of glycine receptors in ventrobasal thalamus, using immunohistochemical staining against α1 and α2 subunits of rat glycine receptors. Using whole-cell current- and voltage-clamp techniques, we determined the effects of glycine and related amino acids on evoked firing and resting membrane properties of ventrobasal neurons. We compared these effects of glycine- and GABA-receptor antagonists on synaptic inhibition evoked from the medial lemniscus. Values are mean ± s.e.mean.

In microscopic examination, 19 ± 4.3 % of 511 cells (6 sections) stained for the α1 subunit, whereas 30 ± 2.7 % of 555 cells (10 sections) were positive for the α2 subunit. In current-clamp experiments, exogenously applied glycine, taurine and β-alanine increased membrane conductance. These effects reversed near ECl and were antagonized by strychnine, indicative of functional glycine receptors. Glycine application decreased input resistance with an EC50 of 126 ± 19 µM and Hill slope of 2.3 ± 0.8 (n = 11). Taurine application decreased input resistance with EC50 of 590 ± 124 µM and slope of 2.0 ± 0.7 (n = 5). β-Alanine application decreased input resistance with EC50 of 703 ± 245 µM and slope of 1.1 ± 0.5 (n = 12). Strychnine, a glycine receptor antagonist, attenuated inhibitory postsynaptic potentials and currents (IPSPs and IPSCs), evoked by high-threshold stimulation of medial lemniscus in two-thirds of neurons (n = 27). For complete blockade, the majority of the IPSPs required co-application of strychnine with bicuculline or gabazine, GABAA receptor antagonists. Strychnine antagonism of residual inhibitory responses during GABAA receptor blockade showed an IC50 of ~ 33 nM (n = 13).

Glycine receptors contribute to synaptic inhibition in rat ventrobasal thalamus.

Dumoulin A, Triller A, and Dieudonné S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21: 6045-6057.
Kim U, Sanchez-Vives MV, and McCormick DA (1997) Functional dynamics of GABAergic inhibition in the thalamus. Science 278: 130-134.