When experiencing or learning, some plastic changes occur in synapses and drive AMPA receptors (AMPA-Rs) into postsynaptic membrane. Moreover, interruption of AMPA-Rs trafficking into synapse disrupts newly learning. These studies establish that AMPA-Rs work as a key molecular machinery underlying experience and learning.
Recent studies using postmortem brains revealed the quantitative alteration of AMPA-Rs may relate to some variety of mental disorders including schizophrenia, depression and ASD. Among these studies, membrane numbers of AMPA-Rs seem to account for these disorders. However, with the current techniques, we cannot observe the behavior of AMPA-Rs in living human brains. Our study aim to develop new PET probes to detect the membrane numbers of AMPA-Rs in living human brains.
We disclosed that animals experiencing inhibitory avoidance (IA) task increase the membrane surface expressions of AMPA-Rs up to 1.5-fold of control animals in the hippocampus. To detect these changes in vivo, we developed new method using LC/MS-MS. Briefly, we administered compounds previously known to bind to AMPA-Rs specifically to adult rats intravenously. 24 hours later, we dissected hippocampus and measure these compounds in the hippocampus using LC/MS-MS. Then we analyze the correlation between biochemical data and MS data.
As a result, some compounds increased in IA+ animals compared to control animals. These results indicate that these compounds detect the increase of surface expression of AMPA-Rs in vivo.