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Excitatory Synaptic Drive and Feedforward Inhibition in the Hippocampal CA3 Circuit Are Regulated by SynCAM 1
- Source :
- Journal of Neuroscience. 36:7464-7475
- Publication Year :
- 2016
- Publisher :
- Society for Neuroscience, 2016.
-
Abstract
- Select adhesion proteins control the development of synapses and modulate their structural and functional properties. Despite these important roles, the extent to which different synapse-organizing mechanisms act across brain regions to establish connectivity and regulate network properties is incompletely understood. Further, their functional roles in different neuronal populations remain to be defined. Here, we applied diffusion tensor imaging (DTI), a modality of magnetic resonance imaging (MRI), to map connectivity changes in knock-out (KO) mice lacking the synaptogenic cell adhesion protein SynCAM 1. This identified reduced fractional anisotropy in the hippocampal CA3 area in absence of SynCAM 1. In agreement, mossy fiber refinement in CA3 was impaired in SynCAM 1 KO mice. Mossy fibers make excitatory inputs onto postsynaptic specializations of CA3 pyramidal neurons termed thorny excrescences and these structures were smaller in the absence of SynCAM 1. However, the most prevalent targets of mossy fibers are GABAergic interneurons and SynCAM 1 loss unexpectedly reduced the number of excitatory terminals onto parvalbumin (PV)-positive interneurons in CA3. SynCAM 1 KO mice additionally exhibited lower postsynaptic GluA1 expression in these PV-positive interneurons. These synaptic imbalances in SynCAM 1 KO mice resulted in CA3 disinhibition, in agreement with reduced feedforward inhibition in this network in the absence of SynCAM 1-dependent excitatory drive onto interneurons. In turn, mice lacking SynCAM 1 were impaired in memory tasks involving CA3. Our results support that SynCAM 1 modulates excitatory mossy fiber inputs onto both interneurons and principal neurons in the hippocampal CA3 area to balance network excitability. SIGNIFICANCE STATEMENT This study advances our understanding of synapse-organizing mechanisms on two levels. First, the data support that synaptogenic proteins guide connectivity and can function in distinct brain regions even if they are expressed broadly. Second, the results demonstrate that a synaptogenic process that controls excitatory inputs to both pyramidal neurons and interneurons can balance excitation and inhibition. Specifically, the study reveals that hippocampal CA3 connectivity is modulated by the synapse-organizing adhesion protein SynCAM 1 and identifies a novel, SynCAM 1-dependent mechanism that controls excitatory inputs onto parvalbumin-positive interneurons. This enables SynCAM 1 to regulate feedforward inhibition and set network excitability. Further, we show that diffusion tensor imaging is sensitive to these cellular refinements affecting neuronal connectivity.
- Subjects :
- Male
0301 basic medicine
Mossy fiber (hippocampus)
Time Factors
Interneuron
Conditioning, Classical
Immunoglobulins
Neural Inhibition
In Vitro Techniques
Hippocampal formation
GABA Antagonists
Synapse
Mice
03 medical and health sciences
0302 clinical medicine
Postsynaptic potential
Neural Pathways
medicine
Animals
Mice, Knockout
Memory Disorders
biology
Chemistry
musculoskeletal, neural, and ocular physiology
General Neuroscience
Cell Adhesion Molecule-1
Articles
Fear
Synaptic Potentials
CA3 Region, Hippocampal
Mice, Inbred C57BL
Pyridazines
Parvalbumins
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
nervous system
Synapses
biology.protein
Excitatory postsynaptic potential
Female
Cell Adhesion Molecules
Neuroscience
030217 neurology & neurosurgery
Parvalbumin
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....575451431a79c08b5275178c0f5ad7dd