Synaptogenesis by Cholinergic Stimulation of Astrocytes
Pamela J Roqué1, Andrés Barria1, Xiaolu Zhang2
1University of Washington.
Research Square
|February 24, 2023
Summary
Neurons signal astrocytes via acetylcholine, prompting astrocytes to release synaptogenic factors that enhance synapse formation. This discovery reveals a new pathway for neuron-astrocyte-neuron communication and synaptogenesis.
Area of Science:
- Neuroscience
- Cell Biology
- Synaptic Plasticity
Background:
- Astrocytes release synaptogenic factors, but signals controlling their release are poorly understood.
- Neuron-derived signals are hypothesized to stimulate astrocytes, which then signal back to neurons.
- Cholinergic signaling in astrocytes and its role in synaptogenesis require further investigation.
Approach:
- Investigated cholinergic stimulation of astrocytes on synaptogenesis in co-cultured neurons.
- Utilized a system for independent manipulation of astrocyte cholinergic signaling prior to co-culture.
- Assessed the impact of pre-stimulated astrocytes on neuronal synapse formation.
Key Points:
- Cholinergic stimulation of astrocytes increased synaptic protein expression and functional synapse numbers in hippocampal neurons.
- Astrocyte release of thrombospondin-1 (TSP-1) was upregulated by cholinergic stimulation.
- Inhibiting the thrombospondin receptor blocked the increase in neuronal synaptic structures.
Conclusions:
- Identified a novel neuron-astrocyte-neuron communication mechanism involving acetylcholine.
- Cholinergic stimulation of astrocytes leads to increased synaptogenesis via TSP-1.
- Revealed new insights into neurotransmitter receptor roles in astrocytes and astrocyte-modulated synaptogenesis.
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