Astrocytic EphB3 receptors regulate d-serine-gated synaptic plasticity and memory

Area of Science:

• Neuroscience
• Cell Biology
• Synaptic Plasticity

Background:

• NMDA receptors (NMDARs) require co-agonists like d-serine for activation.
• The precise mechanisms of astrocyte-neuron communication regulating synaptic d-serine remain unclear.
• Cell adhesion molecules are implicated in astrocytic and neuronal interactions at synapses.

Purpose of the Study:

• To investigate the role of astrocytic EphB3 receptors and their neuronal partner, ephrinB3, in regulating synaptic function.
• To determine the impact of EphB3 signaling on NMDAR activity, synaptic plasticity, and memory.

Main Methods:

• Acute hippocampal slice electrophysiology in adult mice.
• Stimulation and inhibition of EphB3 receptors.
• Knockdown of astrocytic EphB3 receptors.
• Novel object recognition memory tests.

Main Results:

• EphB3 receptor stimulation increased synaptic d-serine availability and NMDAR activity.
• Inhibition of EphB3 receptors impaired NMDAR activity and LTP, rescued by d-serine.
• Astrocytic EphB3 knockdown mimicked these impairments and caused memory deficits.

Conclusions:

• Astrocytic EphB3 receptors are critical for synaptic NMDAR function in the hippocampus.
• EphB3 signaling in astrocytes regulates activity-dependent synaptic plasticity and memory formation.
• This study elucidates a novel mechanism of astrocyte-neuron communication essential for cognitive processes.