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Divergent in vivo activity of non‐serotonergic and serotonergic VGluT3–neurones in the median raphe region
Author(s) -
Domonkos Andor,
Nikitidou Ledri Litsa,
Laszlovszky Tamás,
Cserép Csaba,
Borhegyi Zsolt,
Papp Edit,
Nyiri Gábor,
Freund Tamás F.,
Varga Viktor
Publication year - 2016
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp272036
Subject(s) - serotonergic , raphe , neuroscience , glutamatergic , population , raphe nuclei , dorsal raphe nucleus , monoaminergic , biology , serotonin , psychology , glutamate receptor , medicine , receptor , environmental health
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.