The polyamine transporter Slc18b1(VPAT) is important for both short and long time memory and for regulation of polyamine content in the brain

• Published in: PLoS genetics 2019-12, Vol.15 (12), p.e1008455-e1008455
• Main Authors: Fredriksson, Robert, Sreedharan, Smitha, Nordenankar, Karin, Alsiö, Johan, Lindberg, Frida A, Hutchinson, Ashley, Eriksson, Anders, Roshanbin, Sahar, Ciuculete, Diana M, Klockars, Anica, Todkar, Aniruddha, Hägglund, Maria G, Hellsten, Sofie V, Hindlycke, Viktoria, Västermark, Åke, Shevchenko, Ganna, Olivo, Gaia, K, Cheng, Kullander, Klas, Moazzami, Ali, Bergquist, Jonas, Olszewski, Pawel K, Schiöth, Helgi B
• Format: Article
• Language: English
• Subjects: Acetylcholine; Animals; Binding sites; Biology and Life Sciences; Brain - metabolism; Calcium Signaling; Calcium signalling; Cation Transport Proteins - genetics; Diazepam; Funding; gamma-Aminobutyric Acid - metabolism; Gene Knockout Techniques; Glutamatergic transmission; Glutamic Acid - metabolism; Locomotion; Long term memory; Long-term potentiation; Maze Learning; Medicine and Health Sciences; Memory; Memory, Long-Term; Memory, Short-Term; Mice; Neuronal Plasticity; Neurosciences; Neurovetenskaper; Pattern recognition; Pharmaceuticals; Pharmacology; Phylogenetics; Physiology; Polyamines; Polyamines - metabolism; Proteins; Self-administration; Social Sciences; Supervision; Synaptic plasticity
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1008455

SLC18B1 is a sister gene to the vesicular monoamine and acetylcholine transporters, and the only known polyamine transporter, with unknown physiological role. We reveal that Slc18b1 knock out mice has significantly reduced polyamine content in the brain providing the first evidence that Slc18b1 is functionally required for regulating polyamine levels. We found that this mouse has impaired short and long term memory in novel object recognition, radial arm maze and self-administration paradigms. We also show that Slc18b1 KO mice have altered expression of genes involved in Long Term Potentiation, plasticity, calcium signalling and synaptic functions and that expression of components of GABA and glutamate signalling are changed. We further observe a partial resistance to diazepam, manifested as significantly lowered reduction in locomotion after diazepam treatment. We suggest that removal of Slc18b1 leads to reduction of polyamine contents in neurons, resulting in reduced GABA signalling due to long-term reduction in glutamatergic signalling.