The Role of Vesicular Glutamate Transporter Type 3 in Social Behavior, with a Focus on the Median Raphe Region

Fazekas, Csilla Lea [Fazekas, Csilla Lea (Neurobiológia), author] Institute of Physiology (UP / UPMS); Laboratory of Behavioural and Stress Studies (IEM / DBN); School of PhD Studies (SU); Török, Bibiána [Szocsics-Török, Bibiána (Biológus), author] Laboratory of Behavioural and Stress Studies (IEM / DBN); Correia, Pedro [Correia, Pedro (Neuroscience), author] Institute of Physiology (UP / UPMS); Laboratory of Behavioural and Stress Studies (IEM / DBN); School of PhD Studies (SU); Chaves, Tiago [Chaves, Tiago (Orvostudomány), author] Institute of Physiology (UP / UPMS); Laboratory of Behavioural and Stress Studies (IEM / DBN); School of PhD Studies (SU); Bellardie, Manon; Sipos, Eszter [Bodóné Sipos, Eszter (Idegtudomány), author] Laboratory of Behavioural and Stress Studies (IEM / DBN); Horváth, Hanga Réka [Horváth, Hanga Réka (Orvostudomány), author] Deparment of Behavioural Neurobiology (IEM); Gaszner, Balázs [Gaszner, Balázs (Neuroanatómia), author] Department of Anatomy (UP / UPMS); Szentágothai Research Centre (UP); Dóra, Fanni [Dóra, Fanni (Neurobiológia), author] Anatómiai, Szövet- és Fejlődéstani Intézet (SU / FM / I); Human Brain Tissue Bank (SU / FM / I / ASZFI_2016); Dobolyi, Árpád [Dobolyi, Árpád (Idegtudomány), author] Department of Physiology and Neurobiology (ELTE / ELU FoS / Bio_I); Anatómiai, Szövet- és Fejlődéstani Intézet (SU / FM / I); Zelena, Dóra ✉ [Zelena, Dóra (Neuroendokrinológia), author] Institute of Physiology (UP / UPMS); Laboratory of Behavioural and Stress Studies (IEM / DBN)

English Article (Journal Article) Scientific
Published: ENEURO 2373-2822 11 (6) Paper: ENEURO.0332-23.2024 , 16 p. 2024
  • SJR Scopus - Medicine (miscellaneous): Q1
Identifiers
Fundings:
  • (TKP2021-EGA-16)
  • (Hungarian Brain Research Program 3.0 (NAP 3.0) 2022–2025)
  • (K141934) Funder: NRDIO
  • (K138763) Funder: NKFIH
  • (K120311) Funder: NKFIH
  • (K134221)
  • (ÚNKP-18-1) Funder: -
Social behavior is important for our well-being, and its dysfunctions impact several pathological conditions. Although the involvement of glutamate is undeniable, the relevance of vesicular glutamate transporter type 3 (VGluT3), a specific vesicular transporter, in the control of social behavior is not sufficiently explored. Since midbrain median raphe region (MRR) is implicated in social behavior and the nucleus contains high amount of VGluT3+ neurons, we compared the behavior of male VGluT3 knock-out (KO) and VGluT3-Cre mice, the latter after chemogenetic MRR-VGluT3 manipulation. Appropriate control groups were included. Behavioral test battery was used for social behavior (sociability, social discrimination, social interaction, resident intruder test) and possible confounding factors (open field, elevated plus maze, Y-maze tests). Neuronal activation was studied by c-Fos immunohistochemistry. Human relevance was confirmed by VGluT3 gene expression in relevant human brainstem areas. VGluT3 KO mice exhibited increased anxiety, social interest, but also aggressive behavior in anxiogenic environment and impaired social memory. For KO animals, social interaction induced lower cell activation in the anterior cingulate, infralimbic cortex, and medial septum. In turn, excitation of MRR-VGluT3+ neurons was anxiolytic. Inhibition increased social interest 24 h later but decreased mobility and social behavior in aggressive context. Chemogenetic activation increased the number of c-Fos+ neurons only in the MRR. We confirmed the increased anxiety-like behavior and impaired memory of VGluT3 KO strain and revealed increased, but inadequate, social behavior. MRR-VGluT3 neurons regulated mobility and social and anxiety-like behavior in a context-dependent manner. The presence of VGluT3 mRNA on corresponding human brain areas suggests clinical relevance.
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2025-04-04 16:00