Behavioral alterations and changes in Ca/calmodulin kinase II levels in the striatum of connexin36 deficient mice

Gap junctions (GJ) are intercellular channels which directly connect the cytoplasm of adjacent cells. GJ allow direct cell-to-cell communication via the diffusion of ions, metabolites and second messengers such as IP3. The connexin36 (Cx36) protein has been detected in GJ between interneurons of the hippocampus, cerebral cortex, striatum, amygdala, the inferior olive, cerebellum and other brain structures, such as the olfactory bulb. Cx36 knockout (Cx36 KO) mice display changes in synchronous network oscillations in the hippocampus, neocortex and inferior olive and exhibit impaired spatial alternation and one-trial object recognition in a Y-maze. Here, we further characterized the behavioral changes induced by Cx36 deficiency in the mouse by using different behavioral measures and experimental procedures. Additionally, we examined the effects of Cx36 deficiency on acetylcholine esterase (AChE) activity and calcium calmodulin kinase II alpha (CaMKII) protein levels in the striatum. The homozygous Cx36 KO mice displayed increased locomotion and running speed in the open-field, reduced object exploration and impaired one-trial object-place recognition. Furthermore, they exhibited more anxiety-like behavior as compared to the heterozygous controls in the light–dark box. Homozygous Cx36 KO mice exhibited reduced CaMKII levels in the striatum as compared to the heterozygous mice. AChE activity in the striatum was not significantly different between groups. The present results suggest that Cx36 deficiency in the mouse leads to reduced CaMKII levels in the striatum and behavioral changes in open-field activity, anxiety-related behavior in the light–dark box and one-trial object-place recognition.

► We characterized behavioral changes induced by Cx36 deficiency in the mouse. ► We examined acetylcholine esterase (AChE) activity in the striatum of Cx36 KO mice. ► Furthermore, calcium calmodulin kinase II alpha (CaMKII) protein levels in the striatum of Cx36 KO mice were measured. ► Cx36 KO mice showed altered emotionality, one-trial object-place memory and striatal CaMKII levels. ► These and previous findings suggest that gap junctions are important for the memorization of novel object information.