title: Increased cell-intrinsic excitability induces synaptic changes in new neurons in the adult dentate gyrus that require Npas4.
abstract: Electrical activity regulates the manner in which neurons mature and form connections to each other. However, it remains unclear whether increased single-cell activity is sufficient to alter the development of synaptic connectivity of that neuron or whether a global increase in circuit activity is necessary. To address this question, we genetically increased neuronal excitability of in vivo individual adult-born neurons in the mouse dentate gyrus via expression of a voltage-gated bacterial sodium channel. We observed that increasing the excitability of new neurons in an otherwise unperturbed circuit leads to changes in both their input and axonal synapses. Furthermore, the activity-dependent transcription factor Npas4 is necessary for the changes in the input synapses of these neurons, but it is not involved in changes to their axonal synapses. Our results reveal that an increase in cell-intrinsic activity during maturation is sufficient to alter the synaptic connectivity of a neuron with the hippocampal circuit and that Npas4 is required for activity-dependent changes in input synapses.
authors: Brain and Cognitive Sciences Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors: Shuyin
authors: S
authors: Sim
authors: Salome
authors: S
authors: Antolin
authors: Chia-Wei
authors: CW
authors: Lin
authors: Yingxi
authors: Y
authors: Lin
authors: Ying-Xi
authors: YX
authors: Lin
authors: Carlos
authors: C
authors: Lois
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology* / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005822:Genetic Vectors / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009154:Mutation / Q000235:genetics; D009415:Nerve Net / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism; D000096922:K Cl- Cotransporters; D000097573:Red Fluorescent Protein
chemical_list: D001426:Bacterial Proteins; D051792:Basic Helix-Loop-Helix Proteins; D000076122:Disks Large Homolog 4 Protein; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; D008164:Luminescent Proteins; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D027981:Symporters; D013779:Tetrodotoxin; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D000096922:K Cl- Cotransporters; D000097573:Red Fluorescent Protein; C501447:Dlg4 protein, mouse; C443666:NaChBac protein, bacteria; C533005:Npas4 protein, mouse; C492244:Viaat protein, mouse; C485184:enhanced green fluorescent protein
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