Abstract
Inhibitory postsynaptic currents (IPSCs) of the thalamic reticular (RT) nucleus are dramatically slower than in the neighboring ventrobasal (VB) neurons. It has been suggested that α3-subunit-containing receptors underlie slow IPSCs in RT neurons, while rapid synaptic currents in the VB nucleus are due to γ-aminobutyric acid A receptors (GABAARs), including the α1-subunit. In our recent study [Barberis et al. (2007) Eur. J. Neurosci., 25, 2726–2740] we have found that profound differences in kinetics of currents mediated by α3β2γ2 and α1β2γ3 receptors resulted from distinct binding and desensitization properties. However, a direct comparison between kinetics of neuronal GABAARs from RT and VB neurons and α3- and α1-subunit-containing receptors has not been made. For this purpose, current responses to ultrafast GABA applications were recorded from patches excised from neurons in VB and RT areas. Deactivation kinetics determined for RT and VB neurons closely resembled that in currents mediated by α3β2γ2 and α1β2γ2 receptors. In RT neurons, currents elicited by non-saturating [GABA] had a remarkably slow onset, a hallmark of α3-subunit-containing receptors. In VB and RT neurons, single-channel currents elicited by brief GABA pulses had similar characteristics to those of α1β2γ2 and α3β2γ2 receptors. However, in stationary conditions, similarity between single-channel currents in neurons and respective recombinant receptors was less apparent. We propose that the non-stationary kinetics of GABAergic currents in VB and RT nuclei mimic that of currents mediated by α1- and α3-subunit-containing receptors. The dissimilarity between stationary kinetics of neuronal and recombinant receptors probably reflects differences between GABAARs mediating phasic and tonic currents in these neurons.
Highlights
Thalamic reticular (RT) inhibitory c-aminobutyric acid (GABA)ergic neurons and thalamocortical excitatory ventrobasal (VB) neurons are fundamental in regulating sensory gating, sleep patterns, and are involved in the mechanism of absence epilepsy (Steriade et al, 1993; von Krosigk et al, 1993; Lee et al, 1994; Huguenard, 1999; Blethyn et al, 2006)
Miniature (m)inhibitory postsynaptic current (IPSC) recorded from VB and RT nuclei show profoundly different kinetics mIPSCs were recorded from neurons localized either in patches from VB cells (in VB) or RT nuclei
The major finding of the present work is that the properties of GABAergic currents in VB and RT neurons largely reproduce the kinetic patterns of responses mediated by GABAA receptors containing a1- and a3-subunits
Summary
Thalamic reticular (RT) inhibitory c-aminobutyric acid (GABA)ergic neurons and thalamocortical excitatory ventrobasal (VB) neurons are fundamental in regulating sensory gating, sleep patterns, and are involved in the mechanism of absence epilepsy (Steriade et al, 1993; von Krosigk et al, 1993; Lee et al, 1994; Huguenard, 1999; Blethyn et al, 2006). The inhibitory synaptic currents (IPSCs) in the RT neurons are the slowest in the CNS (Huntsman & Huguenard, 2000, 2006; Browne et al, 2001), while in neighboring VB neurons IPSCs are markedly faster and undergo a developmental speed up (Huntsman & Huguenard, 2000; Okada et al, 2000; Browne et al, 2001), as in the rest of the brain (Takahashi, 2005). In the RT nucleus, the a3-subunit is abundant during development and in adulthood (Laurie et al, 1992; Pirker et al, 2000; Kralic et al, 2006), and is not affected by deletion of the a1-subunit (Kralic et al, 2006). During early development, the predominant a2-subunit in. Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
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