title: Divergent in vivo activity of non-serotonergic and serotonergic VGluT3-neurones in the median raphe region.
abstract: 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.
  
  
  
  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.
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.|János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary.
authors.forename: Andor
authors.initials: A
authors.lastname: Domonkos
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Litsa
authors.initials: L
authors.lastname: Nikitidou Ledri
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Laszlovszky
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Cserép
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.|Present address: MTA-ELTE-NAP B-Opto-Neuropharmacology Group, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Borhegyi
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Edit
authors.initials: E
authors.lastname: Papp
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Nyiri
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Tamás F
authors.initials: TF
authors.lastname: Freund
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Viktor
authors.initials: V
authors.lastname: Varga
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000502:physiology; D008297:Male; D009474:Neurons / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology; D011903:Raphe Nuclei / Q000502:physiology*; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology*; D050496:Vesicular Glutamate Transport Proteins / Q000502:physiology*
chemical_list: C482103:Slc17a8 protein, rat; D050496:Vesicular Glutamate Transport Proteins; D012701:Serotonin