Motor-Skill Learning Is Dependent on Astrocytic Activity.
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 Ca(2+) 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 Ca(2+) signaling during a reaching task is necessary for motor-skill learning.
Department of Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Ragunathan
R
Padmashri
Department of Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Anand
A
Suresh
Department of Radiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Michael D
MD
Boska
Department of Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Anna
A
Dunaevsky
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D002951:Citrates / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005552:Forelimb; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000187:drug effects / Q000235:genetics; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology*; D009154:Mutation; D011597:Psychomotor Performance / Q000187:drug effects; D018091:Receptors, AMPA / Q000187:drug effects; D012694:Serine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology
D000963:Antimetabolites; D002951:Citrates; D004965:Estrogen Antagonists; D053496:Inositol 1,4,5-Trisphosphate Receptors; C580990:Ip3r2 protein, mouse; D018091:Receptors, AMPA; D013629:Tamoxifen; C007744:fluorocitrate; D012694:Serine