Astroglial nuclear factor-κB regulates learning and memory and synaptic plasticity in female mice

Astrocytes play a pivotal role in regulating synaptic plasticity and synapse formation. The nuclear factor-kappa B (NF-KB) family of transcription factors has recently been demonstrated to be an important modulator of synaptic plasticity and learning/memory. In this study, we investigated the role of astroglial NF-KB in synaptic plasticity and learning/memory using transgenic mice over-expressing an N-terminal truncated form of inhibitor of NF-KB alpha (IκBα) in astrocytes (GFAP-IκBα-dn). We demonstrated that female transgenic mice, but not males, have robust deficits in hippocampal and extra-hippocampal-dependent learning and memory. We also determined that there are significant deficits in LTP and expression of metabotropic glutamate receptor 5 and post-synaptic density protein 95 (PSD95) in female transgenic mice. These findings indicate that astroglial NF-KB is an important regulator of learning/memory and synaptic plasticity.