Steroid Receptor Coactivator 3 Regulates Synaptic Plasticity and Hippocampus-dependent Memory

Area of Science:

• Neuroscience
• Molecular Biology
• Endocrinology

Background:

• Steroid hormones are vital for brain development and function.
• Steroid hormone signaling relies on coactivators, but their CNS roles are understudied.
• Steroid receptor coactivator 3 (SRC3) is a key p160 family member predominantly expressed in the hippocampus.

Purpose of the Study:

• To investigate the function of Steroid Receptor Coactivator 3 (SRC3) in the central nervous system, particularly the hippocampus.
• To elucidate the molecular mechanisms underlying SRC3's role in hippocampal function and learning.

Main Methods:

• Utilized Src3^+/- mice to study hippocampal-dependent functions.
• Assessed short-term and spatial memory.
• Measured long-term potentiation (LTP) at Schaffer Collateral-CA1 synapses.
• Analyzed N-methyl-D-aspartate receptor subunit composition in postsynaptic densities.

Main Results:

• Src3^+/- mice exhibited impaired hippocampus-dependent learning and memory.
• Hippocampal development was unaffected in Src3^+/- mice.
• Deficient learning correlated with impaired LTP and altered N-methyl-D-aspartate receptor composition.
• SRC3's regulation of synaptic plasticity and learning depends on its lysine acetyltransferase activity.

Conclusions:

• SRC3 plays a critical role in hippocampal synaptic plasticity, learning, and memory.
• SRC3's lysine acetyltransferase activity is essential for its function in the hippocampus.
• These findings reveal novel functions of SRC3 in the central nervous system and steroid hormone regulation of brain function.