Chronic neurotrophin-3 strengthens synaptic connections to motoneurons in the neonatal rat

Victor L. Arvanian, Philip J. Horner, Fred H. Gage, Lorne M. Mendell

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

We report that neurotrophin-3 (NT-3), delivered chronically via fibroblasts implanted intrathecally into neonatal rats, can facilitate synaptic transmission in the spinal cord. A small collagen plug containing NT-3-secreting fibroblasts was placed on the exposed dorsal surface of the spinal cord (L1) of 2-d-old rats; controls received β -galactosidase-secreting fibroblasts. After 6 hr to 12 d of survival, synaptic potentials (EPSP) elicited by two synaptic inputs, L5 dorsal root and ventrolateral funiculus (VLF), were recorded intracellularly in L5 motoneurons in vitro. Preparations treated with NT-3 implants exhibited enhanced monosynaptic synaptic transmission from both inputs, which persisted over the entire testing period. Unlike acute enhancement of transmission by NT-3 (Arvanian and Mendell, 2001a), the chronic effect could occur at connections not normally eliciting an NMDA receptor-mediated response at the time of NT-3 exposure. Using susceptibility to blockade of the NMDA receptor by Mg 2+ and APV, we confirmed that chronic treatment with NT-3 did not enhance NMDA receptor activity at these connections. Cords treated with chronic NT-3 also transiently displayed polysynaptic components activated by VLF that were blocked by the NMDA receptor antagonist APV. These novel NMDA receptor-mediated potentials may reflect changes in interneurons near the site of fibroblast implantation. We conclude that chronic NT-3 enhances the potency of segmental and descending projections via mechanisms different from those underlying acute changes.

Original languageEnglish (US)
Pages (from-to)8706-8712
Number of pages7
JournalJournal of Neuroscience
Volume23
Issue number25
DOIs
StatePublished - Sep 24 2003

Keywords

  • Development
  • Genetically engineered fibroblasts
  • Motor neuron
  • NT-3
  • Neonatal rat
  • Neurotrophin
  • Plasticity
  • Spinal cord
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Chronic neurotrophin-3 strengthens synaptic connections to motoneurons in the neonatal rat'. Together they form a unique fingerprint.

Cite this