Dynamic microglial modulation of spatial learning and social behavior.
Microglia are active players in inflammation, but also have important supporting roles in CNS maintenance and function, including modulation of neuronal activity. We previously observed an increase in the frequency of excitatory postsynaptic current in organotypic brain slices after depletion of microglia using clodronate. Here, we describe that local hippocampal depletion of microglia by clodronate alters performance in tests of spatial memory and sociability. Global depletion of microglia by high-dose oral administration of a Csf1R inhibitor transiently altered spatial memory but produced no change in sociability behavior. Microglia depletion and behavior effects were both reversible, consistent with a dynamic role for microglia in the regulation of such behaviors.
Program in Molecular and Cellular Pharmacology, Stony Brook University, New York 11794-8651, United States; Department of Pharmacological Sciences, Stony Brook University, New York 11794-8651, United States.
Luisa
L
Torres
Program in Biochemistry and Cell Biology, Stony Brook University, New York 11794-8651, United States.
Joan
J
Danver
Department of Pharmacological Sciences, Stony Brook University, New York 11794-8651, United States.
Kyungmin
K
Ji
Department of Pharmacological Sciences, Stony Brook University, New York 11794-8651, United States.
Jeremy T
JT
Miyauchi
Department of Pharmacological Sciences, Stony Brook University, New York 11794-8651, United States.
Danling
D
Chen
Integrated Neuroscience Area, Department of Psychology, Stony Brook University, Stony Brook, New York 11794-2500, United States.
Maria E
ME
Anderson
Plexxikon Inc., Berkeley, CA 94710, United States.
Brian L
BL
West
Integrated Neuroscience Area, Department of Psychology, Stony Brook University, Stony Brook, New York 11794-2500, United States.
John K
JK
Robinson
Program in Molecular and Cellular Pharmacology, Stony Brook University, New York 11794-8651, United States; Department of Pharmacological Sciences, Stony Brook University, New York 11794-8651, United States. Electronic address: styliani-anna.tsirka@stonybrook.edu.
Stella E
SE
Tsirka
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004002:Clodronic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D012919:Social Behavior; D065853:Spatial Learning / Q000187:drug effects*
D047428:Protein Kinase Inhibitors; D004002:Clodronic Acid; D016186:Receptor, Macrophage Colony-Stimulating Factor
Clodronate; Csf1 inhibition; Hippocampus; Memory; Microglia depletion