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Hemisynapse Formation Between Target Astrocytes and Cortical Neuron Axons in vitro.
1Institute of Neuro- and Sensory Physiology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Frontiers in Molecular Neuroscience
|April 7, 2022
Summary
Researchers explored inducing neuron-astrocyte synapses by overexpressing LRRTM2 in astrocytes. This led to hemisynapse formation, but fully functional synapses required additional factors for proper receptor and vesicle alignment.
Area of Science:
- Neuroscience
- Cell Biology
- Synaptic Plasticity
Background:
- Mammalian brain organization typically prevents direct synaptic connections between neurons and astrocytes.
- Astrocytes express functional ionotropic glutamate receptors, suggesting potential for induced synaptogenesis.
Purpose of the Study:
- To investigate the possibility of inducing synapse formation between co-cultured neurons and astrocytes.
- To determine if overexpressing the synaptogenic protein LRRTM2 in astrocytes can trigger synapse formation.
Main Methods:
- Co-culture of cortical neurons and astrocytes.
- Overexpression of LRRTM2 in astrocytes.
- Assessment of synaptic vesicle clustering using microscopy.
- Whole-cell patch-clamp electrophysiology to record miniature excitatory postsynaptic currents (mEPSCs).
Main Results:
- Control cortical astrocytes spontaneously formed hemisynapses (synaptic vesicle clustering) with contacting axons, correlated with Neuroligin1 expression.
- Overexpression of LRRTM2 enhanced hemisynapse formation in cortical astrocytes.
- Cerebellar astrocytes required LRRTM2 overexpression to induce hemisynapse formation.
- Despite AMPA receptor expression in astrocytes, functional glutamatergic synapses (detectable mEPSCs) were not reliably observed.
Conclusions:
- Overexpression of LRRTM2 successfully induced hemisynapse formation between neurons and astrocytes.
- Fully functional glutamatergic synapses require additional factors beyond LRRTM2 for precise nano-alignment of synaptic components.
