Altered calcium currents and axonal growth in Nf1 haploinsufficient mice

Yuying Wang, Joel M. Brittain, Sarah M. Wilson, Cynthia M. Hingtgen, Rajesh Khanna

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mutations of the neurofibromin gene (NF1) cause neurofibromatosis type 1 (NF1), a disease in which learning disabilities are common. Learning deficits also are observed in mice with a heterozygous mutation of Nf1 (Nf1+/-). Dysregulation of regulated neurotransmitter release has been observed in Nf1+/- mice. However, the role of presynaptic voltage-gated Ca2+ channels mediating this release has not been investigated. We investigated whether Ca2+ currents and transmitter release were affected by reduced neurofibromin in Nf1+/- mice. Hippocampal Ca2+ current density was greater in neurons from Nf1+/- mice and a greater fraction of Ca2+ currents was activated at less depolarized potentials. In addition, release of the excitatory neurotransmitter, glutamate, was increased in neuronal cortical cultures from Nf1+/- mice. Dendritic complexity and axonal length were also increased in neurons Nf1+/- mice compared to wild-type neurons, linking loss of neurofibromin to developmental changes in hippocampal axonal/cytoskeletal dynamics. Collectively, these results show that altered Ca2+ channel density and transmitter release, along with increased axonal growth may account for the abnormal nervous system functioning in NF1.

Original languageEnglish (US)
Pages (from-to)106-114
Number of pages9
JournalTranslational Neuroscience
Volume1
Issue number2
DOIs
StatePublished - Jun 2010
Externally publishedYes

Fingerprint

Neurofibromatosis 1
Neurofibromin 1
Calcium
Growth
Neurons
Neurotransmitter Agents
Mutation
Learning Disorders
Nervous System
Glutamic Acid
Learning
Genes

Keywords

  • Axonal growth
  • Glutamate release
  • Hippocampus
  • N-type calcium channels/CaV2.2
  • Neurofibromin
  • Sholl analysis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Altered calcium currents and axonal growth in Nf1 haploinsufficient mice. / Wang, Yuying; Brittain, Joel M.; Wilson, Sarah M.; Hingtgen, Cynthia M.; Khanna, Rajesh.

In: Translational Neuroscience, Vol. 1, No. 2, 06.2010, p. 106-114.

Research output: Contribution to journalArticle

Wang, Yuying ; Brittain, Joel M. ; Wilson, Sarah M. ; Hingtgen, Cynthia M. ; Khanna, Rajesh. / Altered calcium currents and axonal growth in Nf1 haploinsufficient mice. In: Translational Neuroscience. 2010 ; Vol. 1, No. 2. pp. 106-114.
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