Regulation of GABAergic neurotransmission by purinergic receptors in brain physiology and disease

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Juvenal, Guilherme ; Higa, Guilherme Shigueto Vilar ; Bonfim Marques, Lucas ; Tessari Zampieri, Thais ; Costa Viana, Felipe Jose ; Britto, Luiz R. ; Tang, Yong ; Illes, Peter ; di Virgilio, Francesco ; Ulrich, Henning ; de Pasquale, Roberto

• Document type: Journal article
• Source: PURINERGIC SIGNALLING; v. N/A, p. 29-pg., 2024-07-24.

Abstract

Purinergic receptors regulate the processing of neural information in the hippocampus and cerebral cortex, structures related to cognitive functions. These receptors are activated when astrocytic and neuronal populations release adenosine triphosphate (ATP) in an autocrine and paracrine manner, following sustained patterns of neuronal activity. The modulation by these receptors of GABAergic transmission has only recently been studied. Through their ramifications, astrocytes and GABAergic interneurons reach large groups of excitatory pyramidal neurons. Their inhibitory effect establishes different synchronization patterns that determine gamma frequency rhythms, which characterize neural activities related to cognitive processes. During early life, GABAergic-mediated synchronization of excitatory signals directs the experience-driven maturation of cognitive development, and dysfunctions concerning this process have been associated with neurological and neuropsychiatric diseases. Purinergic receptors timely modulate GABAergic control over ongoing neural activity and deeply affect neural processing in the hippocampal and neocortical circuitry. Stimulation of A2 receptors increases GABA release from presynaptic terminals, leading to a considerable reduction in neuronal firing of pyramidal neurons. A1 receptors inhibit GABAergic activity but only act in the early postnatal period when GABA produces excitatory signals. P2X and P2Y receptors expressed in pyramidal neurons reduce the inhibitory tone by blocking GABAA receptors. Finally, P2Y receptor activation elicits depolarization of GABAergic neurons and increases GABA release, thus favoring the emergence of gamma oscillations. The present review provides an overall picture of purinergic influence on GABAergic transmission and its consequences on neural processing, extending the discussion to receptor subtypes and their involvement in the onset of brain disorders, including epilepsy and Alzheimer's disease. (AU)

• FAPESP's process: 22/00850-3 - Electrophysiological study of serotonergic modulation of the prefrontal cortex during postnatal development
• Grantee: Roberto De Pasquale
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/09277-4 - Hippocampal pathological plasticity in neonatal anoxia
• Grantee: Guilherme Shigueto Vilar Higa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/10950-5 - Selection and evaluation of proteins and fundamental mechanisms for the formation of long-term memory
• Grantee: Guilherme de Araujo Juvenal
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)