SynCAM 1 improves survival of adult‐born neurons by accelerating synapse maturation

The survival of adult‐born dentate gyrus granule cells critically depends on their synaptic integration into the existing neuronal network. Excitatory inputs are thought to increase the survival rate of adult born neurons. Therefore, whether enhancing the stability of newly formed excitatory synapses by overexpressing the synaptic cell adhesion molecule SynCAM 1 improves the survival of adult‐born neurons was tested. Here it is shown that overexpression of SynCAM 1 improves survival of adult‐born neurons, but has no effect on the proliferation rate of precursor cells. As expected, overexpression of SynCAM 1 increased the synapse density in adult‐born granule neurons. While adult‐born granule neurons have very few functional synapses 15 days after birth, it was found that at this age adult‐born neurons in SynCAM 1 overexpressing mice exhibited around three times more excitatory synapses, which were stronger than synapses of adult‐born neurons of control littermates. In summary, the data indicated that additional SynCAM 1 accelerated synapse maturation, which improved the stability of newly formed synapses and in turn increased the likelihood of survival of adult‐born neurons. © 2015 Wiley Periodicals, Inc.

[1]  Magdalena Götz,et al.  Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb , 2013, Proceedings of the National Academy of Sciences.

[2]  T. Südhof,et al.  SynCAM 1 Adhesion Dynamically Regulates Synapse Number and Impacts Plasticity and Learning , 2010, Neuron.

[3]  R. Nicoll,et al.  PSD-95 involvement in maturation of excitatory synapses. , 2000, Science.

[4]  G. Westbrook,et al.  GABAergic signaling to newborn neurons in dentate gyrus. , 2005, Journal of neurophysiology.

[5]  Petter Laake,et al.  Different modes of expression of AMPA and NMDA receptors in hippocampal synapses , 1999, Nature Neuroscience.

[6]  G. Westbrook,et al.  Neuroligin-1 Overexpression in Newborn Granule Cells In Vivo , 2012, PloS one.

[7]  G. Westbrook,et al.  Seizures Accelerate Functional Integration of Adult-Generated Granule Cells , 2006, The Journal of Neuroscience.

[8]  K. Christie,et al.  Regulation of endogenous neural stem/progenitor cells for neural repair—factors that promote neurogenesis and gliogenesis in the normal and damaged brain , 2012, Front. Cell. Neurosci..

[9]  Thomas C. Südhof,et al.  Neuroligins Determine Synapse Maturation and Function , 2006, Neuron.

[10]  Carlo Sala,et al.  Dendritic spines: the locus of structural and functional plasticity. , 2014, Physiological reviews.

[11]  Hongjun Song,et al.  GABA regulates synaptic integration of newly generated neurons in the adult brain , 2006, Nature.

[12]  Fred H. Gage,et al.  NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus , 2006, Nature.

[13]  G. Westbrook,et al.  Neuroligin-1 knockdown reduces survival of adult-generated newborn hippocampal neurons , 2014, Front. Neurosci..

[14]  S. Ge,et al.  A role for primary cilia in glutamatergic synaptic integration of adult-born neurons , 2012, Nature Neuroscience.

[15]  T. Biederer Bioinformatic characterization of the SynCAM family of immunoglobulin-like domain-containing adhesion molecules. , 2006, Genomics.

[16]  A. F. Schinder,et al.  Neuronal Differentiation in the Adult Hippocampus Recapitulates Embryonic Development , 2005, The Journal of Neuroscience.

[17]  F. Gage,et al.  Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons , 2010, Proceedings of the National Academy of Sciences.

[18]  F. Gage,et al.  GABA-cAMP Response Element-Binding Protein Signaling Regulates Maturation and Survival of Newly Generated Neurons in the Adult Hippocampus , 2009, The Journal of Neuroscience.

[19]  F. Gage,et al.  Functional neurogenesis in the adult hippocampus , 2002, Nature.

[20]  F. Gage,et al.  Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus , 1999, Nature Neuroscience.

[21]  M. Dalva,et al.  Cell adhesion molecules: signalling functions at the synapse , 2007, Nature Reviews Neuroscience.

[22]  J. Fiala,et al.  Synaptogenesis Via Dendritic Filopodia in Developing Hippocampal Area CA1 , 1998, The Journal of Neuroscience.

[23]  M. Emerman,et al.  Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus , 1994, Journal of virology.

[24]  T. Biederer,et al.  Expression and adhesion profiles of SynCAM molecules indicate distinct neuronal functions , 2008, The Journal of comparative neurology.

[25]  Arne V. Blackman,et al.  Neuronal morphometry directly from bitmap images , 2014, Nature Methods.

[26]  F. Gage,et al.  Adult neurogenesis and neural stem cells of the central nervous system in mammals , 2002, Journal of neuroscience research.

[27]  Chunmei Zhao,et al.  Distinct Morphological Stages of Dentate Granule Neuron Maturation in the Adult Mouse Hippocampus , 2006, The Journal of Neuroscience.

[28]  X. Leinekugel,et al.  GABAA, NMDA and AMPA receptors: a developmentally regulated `ménage à trois' , 1997, Trends in Neurosciences.

[29]  Jacques I Wadiche,et al.  GABA Depolarization Is Required for Experience-Dependent Synapse Unsilencing in Adult-Born Neurons , 2013, The Journal of Neuroscience.

[30]  V. Stein,et al.  SynCAMs Organize Synapses through Heterophilic Adhesion , 2007, The Journal of Neuroscience.

[31]  C. Rampon,et al.  Long-Term Potentiation Enhances Neurogenesis in the Adult Dentate Gyrus , 2006, The Journal of Neuroscience.

[32]  G. Enikolopov,et al.  Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. , 2010, Cell stem cell.