Neural activity protects hypothalamic magnocellular neurons against axotomy-induced programmed cell death

Tal Shahar, Shirley B. House, Harold Gainer

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Axotomy typically leads to retrograde neuronal degeneration in the CNS. Studies in the hypothalamo-neurohypophysial system (HNS) have suggested that neural activity is supportive of magnocellular neuronal (MCN) survival after axotomy. In this study, we directly test this hypothesis by inhibiting neural activity in the HNS, both in vivo and in vitro, by the use of tetrodotoxin (TTX). After median eminence compression to produce axonal injury, unilateral superfusion of 3 μM TTX into the rat supraoptic nucleus (SON), delivered with the use of a miniature osmotic pump for 2 weeks in vivo, produced a decrease in the number of surviving MCNs in the TTX-treated SON, compared with the contralateral untreated side of the SON. In vitro application of 2.5 μM TTX for 2 weeks to the SON in organotypic culture produced a 73% decrease in the surviving MCNs, compared with untreated control cultures. Raising the extracellular KCl in the culture medium to 25 μM rescued the MCNs from the axotomy- and TTX-induced cell death. These data support the proposal that after axotomy, neural activity is neuroprotective in the HNS.

Original languageEnglish
Pages (from-to)6553-6562
Number of pages10
JournalJournal of Neuroscience
Issue number29
StatePublished - 21 Jul 2004
Externally publishedYes


  • Apoptosis
  • Axotomy
  • Hypothalamus
  • Magnocellular neuron
  • Oxytocin
  • Vasopressin

ASJC Scopus subject areas

  • Neuroscience (all)


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