The article "Extracellular ATP/adenosine dynamics in the brain and its role in health and disease" by Shigetomi, Sakai, and Koizumi reviews the role of extracellular ATP and adenosine in the brain. ATP, a major energy source in the brain, and its metabolite adenosine are key neuromodulators that activate specific receptors, such as P2 receptors (P2X and P2Y) for ATP and P1 receptors (A1, A2A, A2B, A3) for adenosine. These molecules are expressed by both neurons and glial cells, and their regulation is crucial for neuron-glial communication. The authors discuss various methods for measuring extracellular ATP and adenosine, including bioluminescence, HPLC, enzyme-based biosensors, fast-scan cyclic voltammetry, sniffer-cell methods, and fluorescence sensors. They highlight the importance of understanding the spatiotemporal dynamics of these molecules to unravel the complexity of purinergic signaling. The review also covers the mechanisms of ATP and adenosine release from different brain cell types, such as neurons, astrocytes, and microglia. Neurons release ATP from presynaptic terminals and adenosine from postsynaptic sites, while astrocytes release ATP in response to various stimuli and convert it to adenosine. Microglia play a role in detecting and responding to extracellular ATP and adenosine, particularly in pathological conditions like seizures. The authors discuss how ATP and adenosine levels are regulated by multiple pathways, including exocytosis, channel-mediated release, and metabolic processes. In pathological conditions, such as seizures, ischemia, and traumatic brain injury, ATP and adenosine levels are elevated, and their dysregulation contributes to disease pathogenesis. The review highlights the role of purinergic signaling in epilepsy, where adenosine has an anticonvulsant effect, while ATP has a proconvulsant effect. The authors also discuss the potential of using genetically encoded sensors and advanced imaging techniques to better understand the spatiotemporal dynamics of ATP and adenosine in the brain. Overall, the article emphasizes the importance of direct measurement of ATP and adenosine dynamics at the subcellular level to advance our understanding of how purinergic signaling regulates neuron-glial communication in health and disease.The article "Extracellular ATP/adenosine dynamics in the brain and its role in health and disease" by Shigetomi, Sakai, and Koizumi reviews the role of extracellular ATP and adenosine in the brain. ATP, a major energy source in the brain, and its metabolite adenosine are key neuromodulators that activate specific receptors, such as P2 receptors (P2X and P2Y) for ATP and P1 receptors (A1, A2A, A2B, A3) for adenosine. These molecules are expressed by both neurons and glial cells, and their regulation is crucial for neuron-glial communication. The authors discuss various methods for measuring extracellular ATP and adenosine, including bioluminescence, HPLC, enzyme-based biosensors, fast-scan cyclic voltammetry, sniffer-cell methods, and fluorescence sensors. They highlight the importance of understanding the spatiotemporal dynamics of these molecules to unravel the complexity of purinergic signaling. The review also covers the mechanisms of ATP and adenosine release from different brain cell types, such as neurons, astrocytes, and microglia. Neurons release ATP from presynaptic terminals and adenosine from postsynaptic sites, while astrocytes release ATP in response to various stimuli and convert it to adenosine. Microglia play a role in detecting and responding to extracellular ATP and adenosine, particularly in pathological conditions like seizures. The authors discuss how ATP and adenosine levels are regulated by multiple pathways, including exocytosis, channel-mediated release, and metabolic processes. In pathological conditions, such as seizures, ischemia, and traumatic brain injury, ATP and adenosine levels are elevated, and their dysregulation contributes to disease pathogenesis. The review highlights the role of purinergic signaling in epilepsy, where adenosine has an anticonvulsant effect, while ATP has a proconvulsant effect. The authors also discuss the potential of using genetically encoded sensors and advanced imaging techniques to better understand the spatiotemporal dynamics of ATP and adenosine in the brain. Overall, the article emphasizes the importance of direct measurement of ATP and adenosine dynamics at the subcellular level to advance our understanding of how purinergic signaling regulates neuron-glial communication in health and disease.