Journal
FRONTIERS IN NEUROSCIENCE
Volume 14, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2020.604583
Keywords
nicotine; glutamate; synaptic release; calcium imaging; neuronal excitability
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Funding
- DGAPA-PAPIIT (UNAM) [IN216319]
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The rostromedial tegmental nucleus (RMTg) is a bilateral structure in the brainstem mainly composed of GABAergic neurons, which regulates dopamine neurons through glutamatergic and cholinergic inputs. Nicotine was found to induce the persistent release of glutamate in RMTg neurons through the activation of alpha 7 nicotinic acetylcholine receptors and calcium release. This mechanism increases excitability and synchronizes activity of RMTg neurons, suggesting RMTg as a potential therapeutic target for tobacco addiction.
The rostromedial tegmental nucleus (RMTg) is a bilateral structure localized in the brainstem and comprise of mainly GABAergic neurons. One of the main functions of the RMTg is to regulate the activity of dopamine neurons of the mesoaccumbens pathway. Therefore, the RMTg has been proposed as a modulator of the reward system and adaptive behaviors associated to reward learning. The RMTg receives an important glutamatergic input from the lateral habenula. Also, it receives cholinergic inputs from the laterodorsal and pedunculopontine tegmental nuclei. Previously, it was reported that nicotine increases glutamate release, evoked by electric stimulation, in the RMTg nucleus. However, the mechanisms by which nicotine induces this effect were not explored. In the present work, we performed electrophysiological experiments in brainstem slices to study the effect of nicotine on spontaneous excitatory postsynaptic currents recorded from immunocytochemically identified RMTg neurons. Also, we used calcium imaging techniques to explore the effects of nicotine on multiple RMTg neurons simultaneously. We found that nicotine promotes the persistent release of glutamate through the activation of alpha 7 nicotinic acetylcholine receptors present on glutamatergic afferents and by a mechanism involving calcium release from intracellular stores. Through these mechanisms, nicotine increases the excitability and synchronizes the activity of RMTg neurons. Our results suggest that the RMTg nucleus mediates the noxious effects of the nicotine, and it could be a potential therapeutic target against tobacco addiction.
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