Motor-Skill Learning Is Dependent on Astrocytic Activity

• Published in: Journal of neural transplantation & plasticity 2015-01, Vol.2015 (2015), p.512-522-145
• Main Authors: Dunaevsky, Anna, Boska, Michael D., Suresh, Anand, Padmashri, Ragunathan
• Format: Article
• Language: English
• Subjects: Animals; Antimetabolites - pharmacology; Astrocytes; Astrocytes - drug effects; Astrocytes - physiology; Brain; Citrates - pharmacology; Estrogen Antagonists - pharmacology; Experiments; Forelimb; In Vitro Techniques; Injections, Intraventricular; Inositol 1,4,5-Trisphosphate Receptors - drug effects; Inositol 1,4,5-Trisphosphate Receptors - genetics; Laboratories; Learning - drug effects; Learning - physiology; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Mice; Mice, Inbred C57BL; Motor ability; Motor Skills - drug effects; Motor Skills - physiology; Mutation; Neural circuitry; Psychomotor Performance - drug effects; Receptors, AMPA - drug effects; Serine - pharmacology; Spectrum analysis; Stainless steel; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Tamoxifen - pharmacology
• ISSN: 0792-8483; 2090-5904; 1687-5443
• DOI: 10.1155/2015/938023

Motor-skill learning induces changes in synaptic structure and function in the primary motor cortex through the involvement of a long-term potentiation- (LTP-) like mechanism. Although there is evidence that calcium-dependent release of gliotransmitters by astrocytes plays an important role in synaptic transmission and plasticity, the role of astrocytes in motor-skill learning is not known. To test the hypothesis that astrocytic activity is necessary for motor-skill learning, we perturbed astrocytic function using pharmacological and genetic approaches. We find that perturbation of astrocytes either by selectively attenuating IP3R2 mediated astrocyte Ca2+ signaling or using an astrocyte specific metabolic inhibitor fluorocitrate (FC) results in impaired motor-skill learning of a forelimb reaching-task in mice. Moreover, the learning impairment caused by blocking astrocytic activity using FC was rescued by administration of the gliotransmitter D-serine. The learning impairments are likely caused by impaired LTP as FC blocked LTP in slices and prevented motor-skill training-induced increases in synaptic AMPA-type glutamate receptor in vivo. These results support the conclusion that normal astrocytic Ca2+ signaling during a reaching task is necessary for motor-skill learning.