A Serotonin Receptor 1A Containing Complex in Hippocampus of PWD/PhJ Mice is Linked to Training Effects in the Barnes Maze

Although the involvement of the serotonin 1A receptor (5-HT(1A) R) in memory has been shown by several groups there is no information about the 5-HT(1A) R complex but rather the monomeric form. Moreover, there is insufficient information on the characterization of the antigen, the 5-HT(1A) R. PWD/PhJ mice, a wild-caught strain that was inbred at The Jackson Laboratories were used for the experiments. The Barnes maze (BM) paradigm for the evaluation of spatial memory was chosen because of experience with this setting in our laboratory. Mice were sacrificed 6 h following the probe trial on day 12, hippocampi were extirpated, proteins extracted and run on blue native gels with subsequent immunoblotting with a specific antibody against the mouse 5-HT(1A) R. Densitometry of the single band from the immunoblots was carried out. The receptor from the complex was identified by mass spectrometry (nano-LC-ESI-MS/MS). A serotonin receptor 1A complex was identified by immunoblotting at the apparent molecular weight of 480 kDa indicating the presence of a homopolymer as denaturation only revealed a single band at approx. 50 kDa. 5-HT(1A) R levels were significantly higher in the trained group as compared to yoked controls. The hippocampal 5-HT(1A) R of the trained group was unambiguously identified. Taken together, a serotonin receptor 1A homopolymer is associated with memory training effects in the BM using PWD/PhJ mice. This observation shows that a specific complex rather than a receptor subunit as previously shown is involved in memory process and the receptor protein was characterized.