(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.