Astrocytic ankyrin-2 enables memory persistence in the mouse hippocampus.

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Long-term memory persistence is crucial for retaining information.
• Astrocytes play a role in synaptic plasticity, but their mechanisms supporting memory persistence are unknown.
• Ankyrin-2 (Ank2) is a protein found in astrocytes.

Purpose of the Study:

• To investigate the role of astrocytic ankyrin-2 (Ank2) in memory persistence.
• To elucidate the molecular mechanisms by which astrocytes support long-term memory retention.

Main Methods:

• Generated astrocyte-specific Ank2 knockout mice.
• Assessed memory recall using behavioral tests (remote vs. recent memory).
• Investigated synaptic plasticity (long-term potentiation) and astrocyte-neuron interactions.
• Examined brain-derived neurotrophic factor (BDNF) signaling pathways involving TrkB.T1 and IP3R2.

Main Results:

• Astrocyte-specific deletion of Ank2 impaired remote memory but not recent memory.
• Loss of Ank2 disrupted long-term potentiation maintenance.
• Ank2 deficiency reduced astrocyte contacts with engram neurons and impaired astrocyte morphogenesis.
• BDNF signaling via TrkB.T1 and IP3R2 was impaired in Ank2-deficient astrocytes.
• Astrocytic Ank2 was essential for BDNF-induced memory persistence enhancement.
• Activating astrocytic TrkB.T1 signaling was sufficient to enhance remote memory.

Conclusions:

• Astrocytic ankyrin-2 (Ank2) is essential for long-term memory persistence in adult mice.
• Ank2 regulates memory persistence by modulating astrocyte-neuron interactions and BDNF signaling.
• Targeting astrocytic BDNF signaling represents a potential strategy for enhancing memory.