Early postnatal plasticity in neocortex of Fmr1 knockout mice.
Fragile X syndrome is produced by a defect in a single X-linked gene, called Fmr1, and is characterized by abnormal dendritic spine morphologies with spines that are longer and thinner in neocortex than those from age-matched controls. Studies using Fmr1 knockout mice indicate that spine abnormalities are especially pronounced in the first month of life, suggesting that altered developmental plasticity underlies some of the behavioral phenotypes associated with the syndrome. To address this issue, we used intracellular recordings in neocortical slices from early postnatal mice to examine the effects of Fmr1 disruption on two forms of plasticity active during development. One of these, long-term potentiation of intrinsic excitability, is intrinsic in expression and requires mGluR5 activation. The other, spike timing-dependent plasticity, is synaptic in expression and requires N-methyl-d-aspartate receptor activation. While intrinsic plasticity was normal in the knockout mice, synaptic plasticity was altered in an unusual and striking way: long-term depression was robust but long-term potentiation was entirely absent. These findings underscore the ideas that Fmr1 has highly selective effects on plasticity and that abnormal postnatal development is an important component of the disorder.
Desai
Niraj S
NS
The Neurosciences Fine Institute, San Diego, CA 92121, USA. desai@nsi.edu
Casimiro
Tanya M
TM
Gruber
Stephen M
SM
Vanderklish
Peter W
PW
D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000502:physiology*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000502:physiology*; D005600:Fragile X Syndrome / Q000235:genetics / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019579:Neocortex / Q000254:growth & development* / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
D051860:Fragile X Messenger Ribonucleoprotein 1; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C497684:Fmr1 protein, mouse; C578936:Grm5 protein, mouse