Neuronal activity drives IGF2 expression from pericytes to form long-term memory

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Memory research has historically focused on neurons, neglecting other brain cell types.
• Insulin-like growth factor 2 (IGF2) is a polypeptide involved in learning and memory.
• Pericytes are versatile cells in brain microvessels with roles in blood flow, angiogenesis, and the blood-brain barrier.

Purpose of the Study:

• To investigate the cell-type-specific role of hippocampal insulin-like growth factor 2 (IGF2) in memory formation.
• To determine the contribution of pericytes to IGF2 regulation and function in the hippocampus.

Main Methods:

• Utilized rodent models (rats and mice) to study hippocampal IGF2.
• Measured IGF2 levels in different hippocampal cell types, particularly pericytes.
• Examined the impact of learning on pericytic Igf2 expression.
• Performed targeted gene knockout of Igf2 in specific cell types (pericytes, fibroblasts, neurons).
• Assessed long-term memory performance and neuronal immediate early gene (IEG) expression.

Main Results:

• The highest hippocampal IGF2 levels were found in pericytes.
• Learning significantly increased pericytic Igf2 expression in specific hippocampal layers (stratum lacunosum moleculare, stratum moleculare).
• This increase in Igf2 expression was dependent on neuronal activity.
• Knocking out Igf2 in pericytes, but not in fibroblasts or neurons, impaired long-term memory and reduced learning-induced IEG expression.

Conclusions:

• Neuronal activity-driven signaling from pericytes to neurons via IGF2 is essential for long-term memory.
• Pericytes play a critical, previously underappreciated role in regulating memory formation.
• This finding highlights the importance of considering diverse cell types in understanding brain function.