Microglia sense neuronal activity via GABA in the early postnatal hippocampus
Francesca Logiacco1, Pengfei Xia2, Svilen Veselinov Georgiev2
1Cellular Neurosciences, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin, 12169 Berlin, Germany.
Abstract:
Microglia, the resident macrophages in the central nervous system, express receptors for classical neurotransmitters, such as γ-aminobutyric acid (GABA) and glutamate, suggesting that they sense synaptic activity. To detect microglial Ca2+ responses to neuronal activity, we generate transgenic mouse lines expressing the fluorescent Ca2+ indicator GCaMP6m, specifically in microglia and demonstrate that electrical stimulation of the Schaffer collateral pathway results in microglial Ca2+ responses in early postnatal but not adult hippocampus. Preceding the microglial responses, we also observe similar Ca2+ responses in astrocytes, and both are sensitive to tetrodotoxin. Blocking astrocytic glutamate uptake or GABA transport abolishes stimulation-induced microglial responses as well as antagonizing the microglial GABAB receptor. Our data, therefore, suggest that the neuronal activity-induced glutamate uptake and the release of GABA by astrocytes trigger the activation of GABAB receptors in microglia. This neuron, astrocyte, and microglia communication pathway might modulate microglial activity in developing neuronal networks.
Insights
Developing brain microglia respond to neuronal activity via astrocyte-released GABA, activating GABAB receptors. This pathway modulates microglial function in early neural networks.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the brain's immune cells, possess neurotransmitter receptors, indicating a role in sensing neural activity.
- Understanding microglial responses to synaptic activity is crucial for comprehending brain development and function.
Purpose of the Study:
- To investigate microglial calcium (Ca2+) responses to neuronal activity in the developing hippocampus.
- To elucidate the communication pathway involving neurons, astrocytes, and microglia.
Main Methods:
- Generated transgenic mice expressing a calcium indicator (GCaMP6m) in microglia.
- Utilized electrical stimulation of the Schaffer collateral pathway to evoke neuronal activity.
- Measured calcium responses in microglia and astrocytes, and tested the effects of pharmacological blockers.
Main Results:
- Electrical stimulation induced microglial Ca2+ responses in the early postnatal hippocampus, but not in adults.
- Astrocytic Ca2+ responses preceded microglial responses and were sensitive to tetrodotoxin.
- Blocking astrocytic glutamate uptake or GABA transport, or antagonizing microglial GABAB receptors, abolished microglial responses.
Conclusions:
- Astrocytes release GABA in response to neuronal activity, activating microglial GABAB receptors.
- A novel neuron-astrocyte-microglia communication pathway modulates microglial activity during brain development.
- This pathway may play a significant role in shaping developing neural networks.
