The capacity of the brain to acquire and store new information is a sophisticated process whose underlying cellular and molecular mechanisms remain incompletely understood. In the present thesis the role of specific membrane proteins, namely neurotransmitter receptors in the hippocampus, a brain region critically required for spatial learning and memory, was assessed in two related but distinct approaches.
In the first study, the expression of neurotransmitter receptor proteins in hippocampal tissue of mice exposed to a retrieval procedure, assessing the retention of spatial working memory acquired in the Multiple T-maze (MTM) paradigm at several intervals after behavioral training (4, 8, 16 and 30 days), was examined using native blue gel electrophoresis with subsequent Western Blotting.
At the behavioral level, successful memory retrieval at day 8 was paralleled by hippocampal expression of nicotinic acetylcholinergic receptor protein complexes containing the nAChα7-subunit. No behavioral evidence for memory retention indicating extinction of the previously acquired information was observed at day 16 and day 30. Biochemically,hippocampal tissue of mice sacrificed at day 16 and day 30 was found to contain augmented levels of receptor complexes containing the nAChα4 subunit as well as 5HT1A and 5HT7R.
These data suggest a specific relevance of nAChα7-subunit-containing receptor complexes no successful memory retrieval at earlier time points after memory acquisition.
In the second study, focusing on hippocampal long term potentiation (LTP), an in vivo model of learning and memory and behavioral training in spatial learning using the holeboard paradigm was conducted to examine which receptor protein complexes may be employed for the transition of early LTP forms into late LTP. It was observed that behavioral training was sufficient to induce reinforcement of LTP for a period of six hours. At the biochemical level, this was reflected in augmentation of the expression of several neurotransmitter complexes,including those containing glutamatergic (GluN1 and GluN2A, GluA1 and GluA2, and nACh7αR) and dopaminergic (D[1A] dopamine receptor) subunits. In parallel, a reduction of complexes containing the glutamatergic GluA3 and serotonergic 5-HT1A receptor complexes was found in hippocampal tissue of animals after holeboard training. The interaction between GluN1 and D(1A) receptor was analysed using a complex analytical approach based upon antibody shift assays combined with co-immunoprecipitation and mass spectrometry. Hence it is suggested that the behaviourally induced transition from early-LTP into late-LTP may relate to altered levels of specific neurotransmitter complexes in the rat hippocampus.