Fmrp is required for the establishment of the startle response during the critical period of auditory development

Brain Res. 2006 Sep 19;1110(1):159-65. doi: 10.1016/j.brainres.2006.06.086. Epub 2006 Aug 2.

Abstract

Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the FMR-1 gene product FMRP. In addition to the hallmark cognitive defect, other symptoms are also apparent including hyperactivity, seizures and sensory abnormalities including a characteristic increase in sensitivity to auditory, tactile, visual, and olfactory stimuli. Fragile X is a developmental disorder with the first symptoms apparent in the first year of life but little is known about the role of FMRP in developmental processes. The sensory hyperreactivity of fragile X can be reproduced in fmr-1 knockout (KO) mice evident as abnormal audiogenic startle response and increased audiogenic seizure susceptibility. Here, we studied the onset and emergence of the startle deficit in fmr-1 KO mice during development. The startle response was first detectable at the end of the 2nd postnatal week in wild-type mice. The amplitude of startle response showed a substantial increase until the 4th postnatal week followed by a further but moderate increase up to adulthood. Expression of the fmr1 gene was detectable in the startle circuit before the onset and throughout the development of the startle response. Although the onset and amplitude of the startle response were not altered in fmr1 KO mice until the 3rd-4th postnatal week, beyond this age it failed to develop further resulting in an overall response deficit in adult KO mice. This indicates that although Fmrp is dispensable at the initial steps of startle response development, it is necessary for the full development of the response.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acoustic Stimulation / methods
  • Age Factors
  • Analysis of Variance
  • Animals
  • Auditory Pathways / anatomy & histology
  • Auditory Pathways / growth & development*
  • Auditory Pathways / metabolism
  • Behavior, Animal
  • Critical Period, Psychological*
  • Dose-Response Relationship, Radiation
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Mental Retardation Protein / physiology*
  • In Situ Hybridization / methods
  • Mice
  • Mice, Knockout
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reflex, Startle / physiology*
  • Reflex, Startle / radiation effects
  • Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

  • Fmr1 protein, mouse
  • RNA, Messenger
  • Fragile X Mental Retardation Protein