Louis role in regulating AMPA receptor content
GluD1 and 2 have unique characteristics that distinguish them in a synaptic organization. For example, GluD2 has several functions in the PF-PC synapses; regulation of PF-PC formation, the AMPA receptor content, and their LTD. The receptor distribution at synapses PF-PC is lower compared to that at CF-PC. (Kristensen et al., 2016). Deleting GluD2 means the AMPA receptors at PF-PC synapses are overexpressed while the Postsynaptic density Protein (PSD95) increases. Therefore, GluD2 may have a bidirectional effect on synaptic efficacy of PF-PC synapses whereby GluD2 ablation reduces the number of PF-PC synapses but at the same time increases synaptic efficacy by up-regulating GluA1 (Lajtha et al., 2009). Understanding this phenomenon is challenging due to non-existing information relating GluD1 to AMPA receptor regulation. The main role of GluD1 in the cerebellum is associated with AMPA receptors in the development of PF-interneuron synapses.
Regulating GluD1 in different striatal neurons indicates a vital rise in AMPA/NMDA ratio at Pf-MSN receptors. The increasing ratios show the importance of GluD1 in the thalamostriatal synapses, specifically in the cerebellar system (Elender et al., 2013). An example is the action of GluD1 on excitatory synapses. Deletion of the synapses reduces the population of excitatory synapses on MSNs. The research can prove the reduction by observing the miniature excitatory postsynaptic currents (mESPC) frequency and vesicular Glutamate Transporter 2 (vGluT2) puncta (Choy et al., 2018). It shows reduced numbers of thalamic projections, as observed earlier. Therefore, it proves that GluD receptors play an important role in regulating AMPA receptor content.
Suryavanshi et al., 2016 explain the effects of deletion of Glud1, developmental retardation, and a shift of N-methyl-D-aspartate receptor. The features may cause neurodevelopment disorders. On the other hand, GluDs are associated with LTD. In PF-PC long-term depression, GluD2 alters ablation, while in GluD1 KO, the AMPA receptor endocytosis induced by DHPG application is impaired. It is vital to consider that any alteration affecting LTD does not show AMPA content but is only independent features.