Presynaptic release regulating metabotropic receptors: dimerization and receptor cross talk

The Class C subfamily of the G protein coupled receptor (GPCR) family is one of the most important in the central nervous system (CNS), and includes the glutamatergic and GABAergic metabotropic receptors (mGlu and GABAB). The mGlu receptors are fundamental in modulating the efficiency of chemical neurotransmission in the CNS and, as a consequence, they are also involved in several neurological and neurodegenerative disorders. Recently, dimerization of these receptors has become an important topic of investigation and it has been proposed to be crucial to physio-pathological processes in the CNS, as well as to the impact of therapeutics in patients. In this thesis, I will discuss the basic properties of Class C GPCRs focusing on the first and second group of mGlu receptors (Group I and II) and their possible dimerization and/or cross talk with other receptors. I will focus on recent findings concerning these processes that have been mainly obtained by using purified isolated nerve endings (here referred to as synaptosomes), a subcellular preparation of choice for studying presynaptic release regulating receptors. Starting from the pharmacological characterization of Group I and II mGlu receptors, I will then discuss different examples of cross-talk linking these receptors to other ones (i.e. the GABAB and the 5HT2A receptors). I will also show results obtained using electrophysiology to study the role of these receptor subtypes in the modulation of synaptic transmission in hippocampal slices. The resulting picture is undoubtedly complex and highlights how the cross-talk and dimerization of these receptors represent a new frontier in neuropharmacological studies.