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Differential control by 5-HT and 5-HT1A, 2A, 2C receptors of phasic and tonic GABAA inhibition in the visual thalamus

Authors :
Crunelli, Vincenzo
Di Giovanni, Giuseppe
Publication Year :
2015
Publisher :
Wiley-Blackwell Publishing Ltd., 2015.

Abstract

Thalamocortical (TC) neurons, including those of the dorsal lateral geniculate nucleus (dLGN), one of the visual sensory thalamic nuclei, exhibit two forms of GABAA receptor-mediated inhibition: phasic or classical inhibitory postsynaptic currents (IPSCs) generated by the activation of synaptic GABAA receptors (sGABAAR) and tonic inhibition generated by extra- or peri-synaptic GABAA receptors (eGABAAR). The source of GABA mediating tonic inhibition mostly arises from spillover out of the synaptic cleft, because tonic inhibition is blocked by TTX and removal of extracellular Ca2+ in adult murine dLGN TC neurons. Therefore, modulation of vesicular GABA release may not only affect phasic but also tonic inhibition. Previous work in the cat and rat dLGN has shown that several neurotransmitters, including acetylcholine, serotonin (5-HT), dopamine, and norepinephrine can modulate vesicular GABA release from inhibitory interneurons, resulting in changes in phasic inhibition (IPSC frequency), primarily through presynaptic modulation of GABA release from dendro-dendritic synapses [5]. However, except for dopamine in the somatosensory thalamus, the effect of these neurotransmitters on tonic GABAA inhibition in TC neurons has not been examined. Here, we investigated whether 5-HT and its 5-HT1A, 5-HT2A and 5-HT2C receptors exert a control over tonic and phasic GABAA currents in dLGN TC neurons. We used whole cell patch clamp recordings in coronal slices (300 mm) containing the dLGN from postnatal day 20–25 Wistar rats. Data analysis and experimental procedures were similar to those previously described and in accordance with the Animals (Scientific Procedures) Act 1986 (UK). Focal application of gabazine (GBZ, 100 mM) was used to reveal the presence of tonic GABAA current (Figure 1). All serotonergic drugs were dissolved in the recording solution, and their concentrations, co-administration, and effects on phasic and tonic GABAA current are shown in Table 1 and Figure 1. We found that 5-HT enhances phasic GABAA inhibition (i.e., spontaneous IPSCs), but has no action on tonic inhibition. These effects are identical to those observed following 5-HT1A/7R activation with 8-OH-DPAT. On the other hand, α-M-5-HT and mCPP enhances and reduces, respectively, both phasic and tonic GABAA inhibition. These effects are dependent on 5-HT2AR and 5-HT2CR activation, respectively, as they are blocked by co-perfusion with selective antagonists, ketanserin, and SB242084. Thus, the lack of 5-HT modulation of tonic inhibition might be explained by the counterbalance of co-activation of 5-HT2ARs and 5-HT2CRs by the endogenous ligand.<br />peer-reviewed

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.od......3549..fbfe49db543803cce088539254d1e560