| First Author | Liu E | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 5781 |
| PubMed ID | 28720858 | Mgi Jnum | J:250165 |
| Mgi Id | MGI:5926121 | Doi | 10.1038/s41598-017-06173-4 |
| Citation | Liu E, et al. (2017) GSK-3beta deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory. Sci Rep 7(1):5781 |
| abstractText | Increasing evidence suggests that glycogen synthase kinase-3beta (GSK-3beta) plays a crucial role in neurodegenerative/psychiatric disorders, while pan-neural knockout of GSK-3beta also shows detrimental effects. Currently, the function of GSK-3beta in specific type of neurons is elusive. Here, we infused AAV-CaMKII-Cre-2A-eGFP into GSK-3betalox/lox mice to selectively delete the kinase in excitatory neurons of hippocampal dentate gyrus (DG), and studied the effects on cognitive/psychiatric behaviors and the molecular mechanisms. We found that mice with GSK-3beta deletion in DG excitatory neurons displayed spatial and fear memory defects with an anti-anxiety behavior. Further studies demonstrated that GSK-3beta deletion in DG subset inhibited hippocampal synaptic transmission and reduced levels of GluN1, GluN2A and GluN2B (NMDAR subunits), GluA1 (AMPAR subunit), PSD93 and drebrin (postsynaptic structural proteins), and synaptophysin (presynaptic protein). GSK-3beta deletion also suppressed the activity-dependent neural activation and calcium/calmodulin-dependent protein kinase II (CaMKII)/CaMKIV-cAMP response element binding protein (CREB) signaling. Our data suggest that GSK-3beta in hippocampal DG excitatory neurons is essential for maintaining synaptic plasticity and memory. |
