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ZFIN ID: ZDB-PUB-141204-10
Reduced synaptic density and deficient locomotor response in neuronal activity-regulated pentraxin 2a mutant zebrafish
Elbaz, I., Lerer-Goldshtein, T., Okamoto, H., Appelbaum, L.
Date: 2015
Source: FASEB journal : official publication of the Federation of American Societies for Experimental Biology   29(4): 1220-34 (Journal)
Registered Authors: Appelbaum, Lior, Elbaz, Idan, Lerer-Goldshtein, Tali
Keywords: NARP, NPTX2, TALEN, mechanosensory, synaptophysin
MeSH Terms:
  • Acoustic Stimulation
  • Animals
  • Animals, Genetically Modified
  • C-Reactive Protein/deficiency
  • C-Reactive Protein/genetics
  • C-Reactive Protein/physiology*
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Humans
  • Larva/cytology
  • Larva/physiology
  • Mechanotransduction, Cellular
  • Motor Activity
  • Motor Neurons/physiology
  • Nerve Tissue Proteins/deficiency
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/physiology*
  • Neuronal Plasticity/genetics
  • Neuronal Plasticity/physiology*
  • Photic Stimulation
  • Phylogeny
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Zebrafish/anatomy & histology*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 25466900 Full text @ FASEB J.
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ABSTRACT
Neuronal-activity-regulated pentraxin (NARP/NPTX2/NP2) is a secreted synaptic protein that regulates the trafficking of glutamate receptors and mediates learning, memory, and drug addiction. The role of NPTX2 in regulating structural synaptic plasticity and behavior in a developing vertebrate is indefinite. We characterized the expression of nptx2a in larvae and adult zebrafish and established a transcription activator-like effector nuclease (TALEN)-mediated nptx2a mutant (nptx2a(-/-)) to study the role of Nptx2a in regulating structural synaptic plasticity and behavior. Similar to mammals, the zebrafish nptx2a was expressed in excitatory neurons in the brain and spinal cord. Its expression was induced in response to a mechanosensory stimulus but did not change during day and night. Behavioral assays showed that loss of Nptx2a results in reduced locomotor response to light-to-dark transition states and to a sound stimulus. Live imaging of synapses using the transgenic nptx2a:GAL4VP16 zebrafish and a fluorescent presynaptic synaptophysin (SYP) marker revealed reduced synaptic density in the axons of the spinal motor neurons and the anterodorsal lateral-line ganglion (gAD), which regulate locomotor activity and locomotor response to mechanosensory stimuli, respectively. These results suggest that Nptx2a affects locomotor response to external stimuli by mediating structural synaptic plasticity in excitatory neuronal circuits.
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