Astrocytic neurotransmitter receptors (astro‑glioreceptors) and their role in neuroplasticity

Abstract

Astrocytes express a set of neurotransmitter receptors (glioreceptors) that enable them to regulate synaptic transmission and neuroplasticity, and to function as integral partners in synaptic signaling and the modification of neural circuits. This review presents the current understanding of how glioreceptors on astrocytes (astro‑gliorecptors) mediate bidirectional communication between neurons and glia across major neurotransmitter systems. The review focuses on receptors for glutamate, GABA, acetylcholine, monoamines, neuropeptides, opioids, and purines. Through these receptors, astrocytes can modulate synaptic strength, LTP and LTD expression, network dynamics, and state‑dependent modulation of arousal and reward circuits. Despite potentially having lower receptor density than neurons, astrocytes can amplify their functional impact through unique structural properties, such as extensive process arborisation, contact with thousands of synapses, and the formation of electrically coupled syncytia that propagate calcium waves across neural networks. Metabolic integration via glycogen regulation, lactate production, and gliotransmitter release modulates neuronal excitability and synaptic strength. Therefore, astrocytes can be viewed as integrators of neuronal activity patterns and gatekeepers of experience‑dependent plasticity, essential for maintaining synaptic homeostasis and enabling adaptive behavioral responses. Astro‑glioreceptors dysfunctions contribute to neurological and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, epilepsy, and depression. Therefore, targeting specific glioreceptor subtypes represents a promising therapeutic strategy for modulating neural circuits while minimizing neuronal side effects.