title: Astrocytes contribute to gamma oscillations and recognition memory.
abstract: Glial cells are an integral part of functional communication in the brain. Here we show that astrocytes contribute to the fast dynamics of neural circuits that underlie normal cognitive behaviors. In particular, we found that the selective expression of tetanus neurotoxin (TeNT) in astrocytes significantly reduced the duration of carbachol-induced gamma oscillations in hippocampal slices. These data prompted us to develop a novel transgenic mouse model, specifically with inducible tetanus toxin expression in astrocytes. In this in vivo model, we found evidence of a marked decrease in electroencephalographic (EEG) power in the gamma frequency range in awake-behaving mice, whereas neuronal synaptic activity remained intact. The reduction in cortical gamma oscillations was accompanied by impaired behavioral performance in the novel object recognition test, whereas other forms of memory, including working memory and fear conditioning, remained unchanged. These results support a key role for gamma oscillations in recognition memory. Both EEG alterations and behavioral deficits in novel object recognition were reversed by suppression of tetanus toxin expression. These data reveal an unexpected role for astrocytes as essential contributors to information processing and cognitive behavior.
authors: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037;Department of Life Sciences, Sogang University, Mapo-gu, Seoul 121-742, Republic of Korea; hslee@sogang.ac.kr heinemann@salk.edu.
authors: Hosuk Sean
authors: HS
authors: Lee
authors: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037; hslee@sogang.ac.kr heinemann@salk.edu.
authors: Andrea
authors: A
authors: Ghetti
authors: Howard Hughes Medical Institute, Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037;Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal;Neurosciences Unit, Institute of Molecular Medicine, University of Lisbon, 1649-028 Lisbon, Portugal;
authors: António
authors: A
authors: Pinto-Duarte
authors: Howard Hughes Medical Institute, Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037;
authors: Xin
authors: X
authors: Wang
authors: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037;
authors: Gustavo
authors: G
authors: Dziewczapolski
authors: Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037;Department of Biomedical Sciences/Istituto Nazionale di Biostrutture e Biosistemi, University of Sassari Medical School, 07100 Sassari, Italy; and.
authors: Francesco
authors: F
authors: Galimi
authors: Mouse Behavioral Assessment Core, The Scripps Research Institute, La Jolla, CA 92037;
authors: Salvador
authors: S
authors: Huitron-Resendiz
authors: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037;
authors: Juan C
authors: JC
authors: Piña-Crespo
authors: Mouse Behavioral Assessment Core, The Scripps Research Institute, La Jolla, CA 92037;
authors: Amanda J
authors: AJ
authors: Roberts
authors: Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037;
authors: Inder M
authors: IM
authors: Verma
authors: Howard Hughes Medical Institute, Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037;Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors: Terrence J
authors: TJ
authors: Sejnowski
authors: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037; hslee@sogang.ac.kr heinemann@salk.edu.
authors: Stephen F
authors: SF
authors: Heinemann
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling; D002217:Carbachol / Q000494:pharmacology; D004569:Electroencephalography; D015870:Gene Expression; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008959:Models, Neurological; D009415:Nerve Net / Q000166:cytology / Q000502:physiology; D021641:Recognition, Psychology / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission; D013744:Tetanus Toxin / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D013744:Tetanus Toxin; C035979:tetanospasmin; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002217:Carbachol; D008666:Metalloendopeptidases
keywords: electroencephalogram; glia; glial fibrillary acidic protein; gliotransmitter; network oscillation