Divergent in vivo activity of non-serotonergic and serotonergic VGluT3–neurones in the median raphe region

Andor Domonkos, Litsa Nikitidou Ledri, Tamás Laszlovszky, Csaba Cserép, Z. Borhegyi, Edit Papp, G. Nyíri, T. Freund, V. Varga

Research output: Article

2 Citations (Scopus)

Abstract

Key points: The median raphe is a key subcortical modulatory centre involved in several brain functions, such as regulation of the sleep–wake cycle, emotions and memory storage. A large proportion of median raphe neurones are glutamatergic and implement a radically different mode of communication compared to serotonergic cells, although their in vivo activity is unknown. We provide the first description of the in vivo, brain state-dependent firing properties of median raphe glutamatergic neurones identified by immunopositivity for the vesicular glutamate transporter type 3 (VGluT3) and serotonin (5-HT). Glutamatergic populations (VGluT3+/5-HT– and VGluT3+/5-HT+) were compared with the purely serotonergic (VGluT3–/5-HT+ and VGluT3–/5-HT–) neurones. VGluT3+/5-HT+ neurones fired similar to VGluT3–/5-HT+ cells, whereas they significantly diverged from the VGluT3+/5-HT– population. Activity of the latter subgroup resembled the spiking of VGluT3–/5-HT– cells, except for their diverging response to sensory stimulation. The VGluT3+ population of the median raphe may broadcast rapidly varying signals on top of a state-dependent, tonic modulation. Abstract: Subcortical modulation is crucial for information processing in the cerebral cortex. Besides the canonical neuromodulators, glutamate has recently been identified as a key cotransmitter of numerous monoaminergic projections. In the median raphe, a pure glutamatergic neurone population projecting to limbic areas was also discovered with a possibly novel, yet undetermined function. In the present study, we report the first functional description of the vesicular glutamate transporter type 3 (VGluT3)-expressing median raphe neurones. Because there is no appropriate genetic marker for the separation of serotonergic (5-HT+) and non-serotonergic (5-HT–) VGluT3+ neurones, we utilized immunohistochemistry after recording and juxtacellular labelling in anaesthetized rats. VGluT3+/5-HT– neurones fired faster, more variably and were permanently activated during sensory stimulation, as opposed to the transient response of the slow firing VGluT3–/5-HT+ subgroup. VGluT3+/5-HT– cells were also more active during hippocampal theta. In addition, the VGluT3–/5-HT– population, comprising putative GABAergic cells, resembled the firing of VGluT3+/5-HT– neurones but without any significant reaction to the sensory stimulus. Interestingly, the VGluT3+/5-HT+ group, spiking slower than the VGluT3+/5-HT– population, exhibited a mixed response (i.e. the initial transient activation was followed by a sustained elevation of firing). Phase coupling to hippocampal and prefrontal slow oscillations was found in VGluT3+/5-HT– neurones, also differentiating them from the VGluT3+/5-HT+ subpopulation. Taken together, glutamatergic neurones in the median raphe may implement multiple, highly divergent forms of modulation in parallel: a slow, tonic mode interrupted by sensory-evoked rapid transients, as well as a fast one capable of conveying complex patterns influenced by sensory inputs.

Original languageEnglish
Pages (from-to)3775-3790
Number of pages16
JournalJournal of Physiology
Volume594
Issue number13
DOIs
Publication statusPublished - júl. 1 2016

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Vesicular Glutamate Transport Proteins
Serotonin
Neurons
Population

ASJC Scopus subject areas

  • Physiology

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Divergent in vivo activity of non-serotonergic and serotonergic VGluT3–neurones in the median raphe region. / Domonkos, Andor; Nikitidou Ledri, Litsa; Laszlovszky, Tamás; Cserép, Csaba; Borhegyi, Z.; Papp, Edit; Nyíri, G.; Freund, T.; Varga, V.

In: Journal of Physiology, Vol. 594, No. 13, 01.07.2016, p. 3775-3790.

Research output: Article

Domonkos, Andor ; Nikitidou Ledri, Litsa ; Laszlovszky, Tamás ; Cserép, Csaba ; Borhegyi, Z. ; Papp, Edit ; Nyíri, G. ; Freund, T. ; Varga, V. / Divergent in vivo activity of non-serotonergic and serotonergic VGluT3–neurones in the median raphe region. In: Journal of Physiology. 2016 ; Vol. 594, No. 13. pp. 3775-3790.
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T1 - Divergent in vivo activity of non-serotonergic and serotonergic VGluT3–neurones in the median raphe region

AU - Domonkos, Andor

AU - Nikitidou Ledri, Litsa

AU - Laszlovszky, Tamás

AU - Cserép, Csaba

AU - Borhegyi, Z.

AU - Papp, Edit

AU - Nyíri, G.

AU - Freund, T.

AU - Varga, V.

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