Astrocytes contribute to remote memory formation by modulating hippocampal-cortical communication during learning.

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Memory Research

Background:

• Remote memory relies on hippocampus and frontal cortex interactions, with unclear timelines.
• The role of astrocytes in remote memory processing remains largely unexplored.

Purpose of the Study:

• To investigate the role of astrocytes in the CA1 region of the hippocampus during remote memory formation and recall.
• To elucidate the specific neural circuits and communication pathways modulated by astrocytes in memory consolidation.

Main Methods:

• Utilized a chemogenetic approach (hM4Di) to manipulate CA1 astrocyte activity in mice during memory learning.
• Measured neuronal activity in the anterior cingulate cortex (ACC) and CA1-hippocampus during memory retrieval.
• Assessed memory recall for recent and remote memories.
• Investigated CA3-CA1 communication and CA1-to-ACC neuronal pathways.

Main Results:

• Hippocampal astrocyte manipulation during learning selectively impaired remote memory recall, not recent memory.
• This manipulation reduced ACC neuronal activity during memory retrieval.
• Astrocytic G_i activation disrupted CA3-CA1 communication and reduced downstream ACC activation.
• Inhibition of CA1-to-ACC projecting neurons during learning prevented ACC recruitment and impaired remote memory.

Conclusions:

• Astrocytes in the CA1 hippocampus play a critical role in remote memory acquisition.
• Remote memory formation involves projection-specific astrocyte functions regulating CA1-to-ACC neuronal communication.
• Astrocytes modulate neural circuit activity critical for consolidating and retrieving long-term memories.