title: NeuroD2 regulates the development of hippocampal mossy fiber synapses.
abstract: BACKGROUND
  The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF) synapse.
  
  
  RESULTS
  Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice.
  
  
  CONCLUSIONS
  These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.
authors.affiliation: Neurobiology Section, Division of Biological Sciences, University of California, San Diego, CA 92093-0366, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Wilke
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Hall
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Antonios
authors.forename: Laura A
authors.initials: LA
authors.lastname: Denardo
authors.forename: Stefanie
authors.initials: S
authors.lastname: Otto
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.forename: Fading
authors.initials: F
authors.lastname: Chen
authors.forename: Elissa M
authors.initials: EM
authors.lastname: Robbins
authors.forename: Katie
authors.initials: K
authors.lastname: Tiglio
authors.forename: Megan E
authors.initials: ME
authors.lastname: Williams
authors.forename: Zilong
authors.initials: Z
authors.lastname: Qiu
authors.forename: Thomas
authors.initials: T
authors.lastname: Biederer
authors.forename: Anirvan
authors.initials: A
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000235:genetics* / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D013569:Synapses / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009479:Neuropeptides; C098995:Neurod2 protein, mouse