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Non-neuronal, slow GABA signalling in the ventrobasal thalamus targets δ-subunit-containing GABAA receptors

By Cristina Jiménez-González, Tiina Pirttimaki, David W Cope and H R Parri


The rodent ventrobasal (VB) thalamus contains a relatively uniform population of thalamocortical (TC) neurons that receive glutamatergic input from the vibrissae and the somatosensory cortex, and inhibitory input from the nucleus reticularis thalami (nRT). In this study we describe γ-aminobutyric acid (GABA)A receptor-dependent slow outward currents (SOCs) in TC neurons that are distinct from fast inhibitory postsynaptic currents (IPSCs) and tonic currents. SOCs occurred spontaneously or could be evoked by hypo-osmotic stimulus, and were not blocked by tetrodotoxin, removal of extracellular Ca2+ or bafilomycin A1, indicating a non-synaptic, non-vesicular GABA origin. SOCs were more common in TC neurons of the VB compared with the dorsal lateral geniculate nucleus, and were rarely observed in nRT neurons, whilst SOC frequency in the VB increased with age. Application of THIP, a selective agonist at δ-subunit-containing GABAA receptors, occluded SOCs, whereas the benzodiazepine site inverse agonist β-CCB had no effect, but did inhibit spontaneous and evoked IPSCs. In addition, the occurrence of SOCs was reduced in mice lacking the δ-subunit, and their kinetics were also altered. The anti-epileptic drug vigabatrin increased SOC frequency in a time-dependent manner, but this effect was not due to reversal of GABA transporters. Together, these data indicate that SOCs in TC neurons arise from astrocytic GABA release, and are mediated by δ-subunit-containing GABAA receptors. Furthermore, these findings suggest that the therapeutic action of vigabatrin may occur through the augmentation of this astrocyte–neuron interaction, and highlight the importance of glial cells in CNS (patho) physiology

Topics: Synaptic Mechanisms
Publisher: Blackwell Publishing Ltd
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Provided by: PubMed Central

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  16. (1997). GABAA receptor-mediated IPSCs in rat thalamic sensory nuclei: patterns of discharge and tonic modulation by GABAB autoreceptors.
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  18. (1986). GABAergic neurons are present in the dorsal column nuclei but not in the ventroposterior complex of rats.
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  20. (1998). Immunoreactivity for the GABA transporter-1 and GABA transporter-3 is restricted to astrocytes in the rat thalamus. A light and electron-microscopic immunolocalization.
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  23. (1987). Local circuit neurons in the rat ventrobasal thalamus – a GABA immunocytochemical study.
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  25. (2007). mGluR5 stimulates gliotransmission in the nucleus accumbens.
  26. (2005). Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus.
  27. (1983). Neural elements containing glutamic acid decarboxylase (GAD) in the dorsal lateral geniculate nucleus of the rat; immunohistochemical studies by light and electron microscopy.
  28. (2004). Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors.
  29. (2007). Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter GAT-1.
  30. (1997). Nucleus-specific chloride homeostasis in rat thalamus.
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  32. (2005). Ovarian cyclelinked changes in GABA(A) receptors mediating tonic inhibition alter seizure susceptibility and anxiety.
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  34. (2002). Pharmacological characterization of a novel cell line expressing human alpha(4)beta(3)delta GABA(A) receptors.
  35. (2006). Pharmacological characterization of agonists at delta-containing GABAA receptors: functional selectivity for extrasynaptic receptors is dependent on the absence of gamma2.
  36. (1996). Plasma concentrations of vigabatrin in epileptic patients.
  37. (2009). Regulation of cortical microcircuits by unitary GABA-mediated volume transmission.
  38. (2001). Spontaneous astrocytic Ca 2+ oscillations in situ drive NMDAR-mediated neuronal excitation.
  39. (2003). Strong, reliable and precise synaptic connections between thalamic relay cells and neurones of the nucleus reticularis in juvenile rats.
  40. (2009). Synaptic depression enables neuronal gain control.
  41. (2007). Synaptic islands defined by the territory of a single astrocyte.
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  46. (1992). The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development.
  47. (2007). The effects of vigabatrin on spike and wave discharges in WAG ⁄ Rij rats.
  48. (2001). The GABA(A) receptor: subunitdependent functions and absence seizures.
  49. (1993). The potential for increasing seizure frequency, relapse, and appearance of new seizure types with vigabatrin.
  50. (1991). The reticular thalamic nucleus (RTN) of the rat: cytoarchitectural, Golgi, immunocytochemical, and horseradish peroxidase study.
  51. (1998). The synaptic basis of GABAA,slow.
  52. (1987). The THIP-induced model of bilateral synchronous spike and wave in rodents.
  53. (1996). Tonic facilitation of glutamate release by presynaptic N-methyl-D-aspartate autoreceptors in the entorhinal cortex.
  54. (2005). Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus.
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  56. (2009). Unconventional GABA release: mechanisms and function.
  57. (1997). Utility of the lethargic (lh ⁄ lh) mouse model of absence seizures in predicting the effects of lamotrigine, vigabatrin, tiagabine, gabapentin, and topiramate against human absence seizures.
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