Tonic activation of presynaptic GABAB receptors on thalamic sensory afferents

Z. Emri, J. P. Turner, V. Crunelli

Research output: Contribution to journalArticle

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Abstract

The presence and role of presynaptic GABAB receptors in the control of excitatory amino acid-mediated transmission were investigated (using sharp electrode recordings) in the rat dorsal lateral geniculate nucleus and ventrobasal thalamus in vitro by comparing the effects of the selective GABAB receptor agonist, (±)-baclofen, and of two antagonists, CGP 35348 and 2-hydroxy-saclofen, on the excitatory postsynaptic potentials evoked in thalamocortical neurons by stimulation of the sensory afferents. Application of CGP 35348 alone blocked the GABAB receptor-mediated inhibitory postsynaptic potential evoked in the dorsal lateral geniculate nucleus by stimulation of the optic tract (n = 5), but had no effect on the resting membrane potential and input resistance of thalamocortical cells (n = 6). In contrast, 2-hydroxy-saclofen caused a hyperpolarization (6.9 ± 0.5 mV, n = 10) and a decrease in the apparent input resistance (26.3 ± 2.6%, n = 10). This effect of 2-hydroxy-saclofen was antagonized by CGP 35348. When bicuculline was present in the perfusion medium and following intracellular injection of QX 314, GABAA and GABAB receptors in the recorded neuron were blocked. Under this condition, application of baclofen decreased the amplitude of the medial lemniscus-and optic tract-evoked excitatory postsynaptic potentials in the two thalamic nuclei investigated. This effect was fully antagonized by CGP 35348 and only partially by 2-hydroxy-saclofen. CGP 35348 alone increased (19.3 ± 4.3%, n = 5) and 2-hydroxy-saclofen alone decreased (29.9 ± 8.6%, n = 5) the amplitude of the excitatory postsynaptic potential. This effect of 2-hydroxy-saclofen was not blocked by CGP 35348. These results indicate that presynaptic GABAB receptors are present on the terminals of the sensory afferents in the rat dorsal lateral geniculate nucleus and in the ventrobasal thalamus. These receptors are tonically activated by endogenous GABA, at least in vitro, and provide a negative control mechanism by which the excitatory amino acid-mediated transmission within these nuclei can be regulated. In contrast, the endogenous GABA level is not sufficient for a tonic activation of postsynaptic GABAB receptors. Furthermore, these results indicate that 2-hydroxy-saclofen acts as a partial agonist on postsynaptic CGP 35348-sensitive GABAB receptors, and that, in addition to its antagonist action on presynaptic CGP 35348-sensitive GABAB receptors, it also has an effect on either presynaptic, CGP 35348-insensitive GABAB receptors and/or another presynaptic receptor type.

Original languageEnglish
Pages (from-to)689-698
Number of pages10
JournalNeuroscience
Volume72
Issue number3
DOIs
Publication statusPublished - Jun 1996

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Presynaptic Receptors
Geniculate Bodies
Excitatory Postsynaptic Potentials
Excitatory Amino Acids
Thalamus
gamma-Aminobutyric Acid
GABA-B Receptors
CGP 35348
Thalamic Nuclei
Inhibitory Postsynaptic Potentials
Baclofen
Bicuculline
Sensory Receptor Cells
GABA-A Receptors
2-hydroxysaclofen
Membrane Potentials
Electrodes
Perfusion
Neurons
Injections

Keywords

  • Baclofen
  • Dorsal lateral geniculate nucleus
  • GABA antagonists
  • Ventrobasal thalamus

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Tonic activation of presynaptic GABAB receptors on thalamic sensory afferents. / Emri, Z.; Turner, J. P.; Crunelli, V.

In: Neuroscience, Vol. 72, No. 3, 06.1996, p. 689-698.

Research output: Contribution to journalArticle

Emri, Z. ; Turner, J. P. ; Crunelli, V. / Tonic activation of presynaptic GABAB receptors on thalamic sensory afferents. In: Neuroscience. 1996 ; Vol. 72, No. 3. pp. 689-698.
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