On the G Protein-Coupled Receptor Neuromodulation of the Claustrum.

G protein-coupled receptors modulate the synaptic glutamate and GABA transmission of the claustrum. The work focused on the transmitter-receptor relationships in the claustral catecholamine system and receptor-receptor interactions between kappa opioid receptors (KOR) and SomatostatinR2 (SSTR2) in claustrum. Methods used involved immunohistochemistry and in situ proximity ligation assay (PLA) using confocal microscopy. Double immunolabeling studies on dopamine (DA) D1 receptor (D1R) and tyrosine hydroxylase (TH) immunoreactivities (IR) demonstrated that D1R IR existed in almost all claustral and dorsal endopiriform nucleus (DEn) nerve cell bodies, known as glutamate projection neurons, and D4R IR in large numbers of nerve cell bodies of the claustrum and DEn. However, only a low to moderate density of TH IR nerve terminals was observed in the DEn versus de few scattered TH IR terminals found in the claustrum. These results indicated that DA D1R and D4R transmission in the rat operated via long distance DA volume transmission in the rat claustrum and DEn to modulate claustral-sensory cortical glutamate transmission. Large numbers of these glutamate projection neurons also expressed KOR and SSTR2 which formed KOR-SSTR2 heteroreceptor complexes using PLA. Such receptor-receptor interactions can finetune the activity of the glutamate claustral-sensory cortex projections from inhibition to enhancement of their sensory cortex signaling. This can give the sensory cortical regions significant help in deciding on the salience to be given to various incoming sensory stimuli.