Altered cognitive performance and synaptic function in the hippocampus of mice lacking C3

Marta Perez-Alcazar; Jonny Daborg; Anna Stokowska; Pontus Wasling; Andreas Björefeldt; Marie Kalm; Henrik Zetterberg; Karl E Carlström; Klas Blomgren; Christine T Ekdahl; Eric Hanse; Marcela Pekna

doi:10.1016/j.expneurol.2013.12.013

Altered cognitive performance and synaptic function in the hippocampus of mice lacking C3

Exp Neurol. 2014 Mar:253:154-64. doi: 10.1016/j.expneurol.2013.12.013. Epub 2013 Dec 28.

Authors

Affiliations

¹ 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.
² Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden.
³ Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at the University of Gothenburg, S-405 30 Gothenburg, Sweden.
⁴ 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.
⁵ Inflammation and Stem Cell Therapy Group, Division of Clinical Neurophysiology, Lund University and Skåne University Hospital, SE-221 84 Lund, Sweden.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ 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.

PMID: 24378428
DOI: 10.1016/j.expneurol.2013.12.013

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.

Keywords: Complement cascade; Development; Epilepsy; Hippocampus; Synapse elimination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Avoidance Learning / physiology
Cognition Disorders / genetics*
Cognition Disorders / pathology
Complement C3 / deficiency*
Disease Models, Animal
Dizocilpine Maleate / pharmacology
Electric Stimulation
Excitatory Amino Acid Antagonists / pharmacology
Excitatory Postsynaptic Potentials / drug effects
Excitatory Postsynaptic Potentials / genetics
GABA Antagonists / pharmacology
Gene Expression Regulation / drug effects
Gene Expression Regulation / genetics
Hippocampus / pathology*
In Vitro Techniques
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Net / pathology
Nerve Net / physiopathology
Neurons / diagnostic imaging
Neurons / drug effects
Neurons / physiology*
Picrotoxin / pharmacology
Synapses / drug effects
Synapses / physiology*
Ultrasonography
Valine / analogs & derivatives
Valine / pharmacology

Substances

Complement C3
Excitatory Amino Acid Antagonists
GABA Antagonists
Picrotoxin
Dizocilpine Maleate
2-amino-5-phosphopentanoic acid
Valine