Somatosensory cortical barrel dendritic abnormalities in a mouse model of the fragile X mental retardation syndrome

Autism as a disorder of neural information processing: directions for research and targets for therapy

“…The fact that there are more long, thin spines, and more spines overall, may reflect a failure of the synapse elimination that would normally occur during early development. A study of the hippocampal formation in idiopathic autism [187] described reduced dendritic field size in pyramidal neurons in the Ammon's horn region, a result that contrasts with the FXS findings (in other brain regions) and suggests either a failure to fully reach adult form (the authors' interpretation) or an increase in the amount of pruning in the autistic cases, the opposite of what is reported in barrel cortex [94]. Either sort of change, an abnormal abundance of dendritic connections or an abnormal lack of them, could lead to difficulty in information processing due to reduced signal-to-noise.…”

“…Knockout of the FMR1 gene in mice increases dendritic spine density in visual cortex [56]. Similarly, in barrel cortex, a natural process of developmental dendritic regression fails to occur in the knockout mouse [94]. Taken together, these findings provide strong evidence for a critical role of FMRP in protein syntheses involved in activity-dependent brain development, and specifically in the patterning of neural circuitry.…”

Mental retardation genes in drosophila: New approaches to understanding and treating developmental brain disorders

“…However, at the single-neuron level (using the Golgi impregnation technique on postmortem brain tissue), cortical neurons in several regions have abnormal dendrites, with spines showing excessive numbers and length [Rudelli et al, 1985;Hinton et al, 1991;Wisniewski et al, 1991;Irwin et al, 2001]. Similar studies in the Fmr1 mutant mouse confirmed these findings, as well as excessive dendritic branching [Comery et al, 1997;Irwin et al, 2002;Galvez et al, 2003]. Given that spines are postsynaptic sites and that dendrites undergo complex alterations during development [Cline, 2001], it is not surprising that a "subtle" morphological change would cause serious functional consequences.…”

Visual Experience Regulates Transient Expression and Dendritic Localization of Fragile X Mental Retardation Protein

“…Although hippocampal LTP is normal, long-term depression in this structure is enhanced in the absence of FMRP (Huber et al, 2002). Finally, abnormalities in synaptic structure are observed in FXS patients, as well as mouse and Drosophila models of this disease (Nimchinsky et al, 2001;Galvez et al, 2003;Lee et al, 2003) The regulation of FMRP expression and localization is likely to be an important control point in synaptic plasticity. Activation of metabotropic glutamate receptors (mGluR) in isolated synaptoneurosomes has been reported to increase both Fmr1 mRNA association with polyribosomes and FMRP expression (Weiler et al, 1997).…”