title: Altered cognitive performance and synaptic function in the hippocampus of mice lacking C3.
abstract: Previous work implicated the complement system in adult neurogenesis as well as elimination of synapses in the developing and injured CNS. In the present study, we used mice lacking the third complement component (C3) to elucidate the role the complement system plays in hippocampus-dependent learning and synaptic function. We found that the constitutive absence of C3 is associated with enhanced place and reversal learning in adult mice. Our findings of lower release probability at CA3-CA1 glutamatergic synapses in combination with unaltered overall efficacy of these synapses in C3 deficient mice implicate C3 as a negative regulator of the number of functional glutamatergic synapses in the hippocampus. The C3 deficient mice showed no signs of spontaneous epileptiform activity in the hippocampus. We conclude that C3 plays a role in the regulation of the number and function of glutamatergic synapses in the hippocampus and exerts negative effects on hippocampus-dependent cognitive performance.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden; Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors.forename: Marta
authors.initials: M
authors.lastname: Perez-Alcazar
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors.forename: Jonny
authors.initials: J
authors.lastname: Daborg
authors.affiliation: Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Stokowska
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Wasling
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Björefeldt
authors.affiliation: Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Kalm
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Inflammation and Stem Cell Therapy Group, Division of Clinical Neurophysiology, Lund University and Skåne University Hospital, SE-221 84 Lund, Sweden.
authors.forename: Karl E
authors.initials: KE
authors.lastname: Carlström
authors.affiliation: Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden; Department of Pediatrics Oncology, University of Gothenburg, The Queen Silvia Children's Hospital, 413 45 Gothenburg, Sweden; Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital Q2:07, 171 76 Stockholm, Sweden.
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
authors.affiliation: Inflammation and Stem Cell Therapy Group, Division of Clinical Neurophysiology, Lund University and Skåne University Hospital, SE-221 84 Lund, Sweden; Lund Epilepsy Center, Dept Clinical Sciences, Lund University, Sweden.
authors.forename: Christine T
authors.initials: CT
authors.lastname: Ekdahl
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden. Electronic address: Eric.Hanse@physiol.gu.se.
authors.forename: Eric
authors.initials: E
authors.lastname: Hanse
authors.affiliation: Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia. Electronic address: Marcela.Pekna@neuro.gu.se.
authors.forename: Marcela
authors.initials: M
authors.lastname: Pekna
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000502:physiology; D003072:Cognition Disorders / Q000235:genetics* / Q000473:pathology; D003176:Complement C3 / Q000172:deficiency*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D018756:GABA Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014463:Ultrasonography; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D003176:Complement C3; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010852:Picrotoxin; D014633:Valine; C056639:2-amino-5-phosphopentanoic acid
keywords: Complement cascade; Development; Epilepsy; Hippocampus; Synapse elimination