The GSK-3 Inhibitor CT99021 Enhances the Acquisition of Spatial Learning and the Accuracy of Spatial Memory

• Published in: Frontiers in molecular neuroscience Vol. 14; p. 804130
• Main Authors: Lee, Yeseul, Bortolotto, Zuner A, Bradley, Clarrisa A, Sanderson, Thomas M, Zhuo, Min, Kaang, Bong-Kiun, Collingridge, Graham L
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 27.01.2022; Frontiers Media S.A
• Subjects: Accuracy; Alzheimer's disease; Behavior; Cameras; CT99021; DMTP T-maze; Experiments; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Glycogen; Glycogen synthase kinase 3; GSK-3; Hippocampus; Laboratory animals; Locomotor activity; Long-term depression; Memory; Morris water maze; N-Methyl-D-aspartic acid receptors; Neuroscience; NMDAR-dependent LTD; Polyethylene glycol; Protein kinase; Reversal learning; Spatial discrimination learning; spatial learning and memory; Spatial memory; Synaptic plasticity; Morris water maze; memory enhancement; DMTP T-maze; CT99021; GSK-3; NMDAR-dependent LTD; spatial learning and memory
• ISSN: 1662-5099; 1662-5099
• DOI: 10.3389/fnmol.2021.804130

Glycogen synthase kinase 3 (GSK-3) is a Ser/Thr protein kinase that regulates many cellular processes, including synaptic plasticity. Previously, we reported that inhibition of GSK-3 prevents the induction of one of the major forms of synaptic plasticity, N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD), in hippocampal slices. In the present study, we have investigated the effects of inhibiting GSK-3 on learning and memory in healthy naïve animals. Systemic administration of a highly selective GSK-3 inhibitor, CT99021, reversibly blocked NMDAR-dependent LTD in the CA1 region of the hippocampus in anesthetized adult mice. In behavioral tasks, CT99021 had no effect on locomotor activity, anxiety, hippocampus-dependent contextual fear memory, and hippocampus-dependent reversal learning. However, CT99021 facilitated the rate of learning in the Morris water maze (MWM) and T-maze and enhanced the accuracy of long-term spatial memory in the MWM. These findings suggest that GSK-3 regulates the accuracy of spatial memory acquisition and recall.