The study investigates the network-level encoding of local neurotransmitter inputs in cortical astrocytes. Astrocytes, the most abundant non-neuronal cells in the mammalian brain, play crucial roles in modulating neuronal activity through calcium (Ca²⁺) signaling. The research uses ex vivo and in vivo two-photon astrocyte imaging to mimic neuronal neurotransmitter inputs at multiple spatiotemporal scales. Key findings include: 1. **Subcellular to Network-Level Responses**: Brief, subcellular inputs of GABA and glutamate lead to widespread, long-lasting astrocyte Ca²⁺ responses beyond the stimulated cell. 2. **Propagative Activity**: A subset of Ca²⁺ activity, called propagative activity, differentiates astrocyte network responses to GABA and glutamate, suggesting a role in integrating information across cellular compartments. 3. **NT-Specific Responses**: Astrocytes exhibit distinct activity patterns in response to different neurotransmitters, with glutamate leading to more dynamic and widespread Ca²⁺ responses compared to GABA. 4. **Gap Junction Coupling**: Gap junction coupling, mediated by connexin 43 (Cx43), contributes to network-wide Ca²⁺ responses, with reduced coupling leading to attenuated network responses. 5. **Context-Dependent Responses**: Astrocyte network responses to neurotransmitters are context-dependent, influenced by the baseline activity state of the network. These findings highlight the complex and distributed nature of astrocyte responses to neurotransmitter inputs, providing insights into how astrocytes integrate and modulate neuronal activity over time and space.The study investigates the network-level encoding of local neurotransmitter inputs in cortical astrocytes. Astrocytes, the most abundant non-neuronal cells in the mammalian brain, play crucial roles in modulating neuronal activity through calcium (Ca²⁺) signaling. The research uses ex vivo and in vivo two-photon astrocyte imaging to mimic neuronal neurotransmitter inputs at multiple spatiotemporal scales. Key findings include: 1. **Subcellular to Network-Level Responses**: Brief, subcellular inputs of GABA and glutamate lead to widespread, long-lasting astrocyte Ca²⁺ responses beyond the stimulated cell. 2. **Propagative Activity**: A subset of Ca²⁺ activity, called propagative activity, differentiates astrocyte network responses to GABA and glutamate, suggesting a role in integrating information across cellular compartments. 3. **NT-Specific Responses**: Astrocytes exhibit distinct activity patterns in response to different neurotransmitters, with glutamate leading to more dynamic and widespread Ca²⁺ responses compared to GABA. 4. **Gap Junction Coupling**: Gap junction coupling, mediated by connexin 43 (Cx43), contributes to network-wide Ca²⁺ responses, with reduced coupling leading to attenuated network responses. 5. **Context-Dependent Responses**: Astrocyte network responses to neurotransmitters are context-dependent, influenced by the baseline activity state of the network. These findings highlight the complex and distributed nature of astrocyte responses to neurotransmitter inputs, providing insights into how astrocytes integrate and modulate neuronal activity over time and space.