Control of Dopamine Signal in High-Order Receptor Complex on Striatal Astrocytes.

The receptor-receptor interaction (RRI) of G protein-coupled receptors (GPCRs) leads to new functional entities that are conceptually distinct from the simple addition of signals mediated by the activation of the receptors that form the heteromers. Focusing on astrocytes, there is evidence for the existence of inhibitory and facilitatory RRIs, including the heteromers formed by the adenosine A2A and the dopamine D2 receptors, by A2A and the oxytocin receptor (OTR), and the D2-OTR heteromers. The possible involvement of these receptors in mosaicism has never been investigated in striatal astrocytes.

A Self-Similarity Logic May Shape the Organization of the Nervous System.

From the morphological point of view, the nervous system exhibits a fractal, self-similar geometry at various levels of observations, from single cells up to cell networks. From the functional point of view, it is characterized by a hierarchical organization in which self-similar structures (networks) of different miniaturizations are nested within each other. In particular, neuronal networks, interconnected to form neuronal systems, are formed by neurons, which operate thanks to their molecular networks, mainly having proteins as components that via protein-protein interactions can be assembled in multimeric complexes working as micro-devices.

Modulation of Neuron and Astrocyte Dopamine Receptors via Receptor-Receptor Interactions.

Dopamine neurotransmission plays critical roles in regulating complex cognitive and behavioral processes including reward, motivation, reinforcement learning, and movement. Dopamine receptors are classified into five subtypes, widely distributed across the brain, including regions responsible for motor functions and specific areas related to cognitive and emotional functions. Dopamine also acts on astrocytes, which express dopamine receptors as well.

Striatal astrocytic A2A-D2 receptor-receptor interactions and their role in neuropsychiatric disorders.

It is now generally accepted that astrocytes are active players in synaptic transmission, so that a neurocentric perspective of the integrative signal communication in the central nervous system is shifting towards a neuro-astrocentric perspective. Astrocytes respond to synaptic activity, release chemical signals (gliotransmitters) and express neurotransmitter receptors (G protein-coupled and ionotropic receptors), thus behaving as co-actors with neurons in signal communication in the central nervous system. The ability of G protein-coupled receptors to physically interact through heteromerization, forming heteromers and receptor mosaics with new distinct signal recognition and transduction pathways, has been intensively studied at neuronal plasma membrane, and has changed the view of the integrative signal communication in the central nervous system.