title: CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype.
abstract: Mounting evidence suggests that voltage-gated L-type Ca2+ channels can modulate affective behaviour. We therefore explored the role of CaV1.3 L-type Ca2+ channels in depression- and anxiety-like behaviours using CaV1.3-deficient mice (CaV1.3-/-). We showed that CaV1.3-/- mice displayed less immobility in the forced swim test as well as in the tail suspension test, indicating an antidepressant-like phenotype. Locomotor activity in the home cage or a novel open-field test was not influenced. In the elevated plus maze (EPM), CaV1.3-/- mice entered the open arms more frequently and spent more time there indicating an anxiolytic-like phenotype which was, however, not supported in the stress-induced hyperthermia test. By performing parallel experiments in Claudin 14 knockout mice (Cldn14-/-), which like CaV1.3-/- mice are congenitally deaf, an influence of deafness on the antidepressant-like phenotype could be ruled out. On the other hand, a similar EPM behaviour indicative of an anxiolytic phenotype was also found in the Cldn14-/- animals. Using electroretinography and visual behavioural tasks we demonstrated that at least in mice, CaV1.3 channels do not significantly contribute to visual function. However, marked morphological changes were revealed in synaptic ribbons in the outer plexiform layer of CaV1.3-/- retinas by immunohistochemistry suggesting a possible role of this channel type in structural plasticity at the ribbon synapse. Taken together, our findings indicate that CaV1.3 L-type Ca2+ channels modulate depression-like behaviour but are not essential for visual function. The findings raise the possibility that selective modulation of CaV1.3 channels could be a promising new therapeutic concept for the treatment of mood disorders.
authors: Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria.
authors: Perrine
authors: P
authors: Busquet
authors: Ngoc Khoi
authors: NK
authors: Nguyen
authors: Eduard
authors: E
authors: Schmid
authors: Naoyuki
authors: N
authors: Tanimoto
authors: Mathias W
authors: MW
authors: Seeliger
authors: Tamar
authors: T
authors: Ben-Yosef
authors: Fengxia
authors: F
authors: Mizuno
authors: Abram
authors: A
authors: Akopian
authors: Jörg
authors: J
authors: Striessnig
authors: Nicolas
authors: N
authors: Singewald
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000235:genetics*; D057167:Claudins; D003638:Deafness / Q000151:congenital / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D004195:Disease Models, Animal; D006979:Hyperthermia, Induced; D046353:Immobility Response, Tonic; D008297:Male; D018782:Maze Learning; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D010641:Phenotype; D012160:Retina / Q000648:ultrastructure; D013569:Synapses / Q000648:ultrastructure
chemical_list: C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D057167:Claudins; D008565:Membrane Proteins; C422064:claudin 14