| Fragile X syndrome, a monogenic, sex-linked, neurodevelopmental disorder, is the most common cause of inherited male mental retardation and a leading genetic indicator of autism. Fragile X is caused by a tri-nucleotide repeat expansion of the FMR1 gene that silences translation of the RNA-binding protein, FMRP. Sensory integration deficits in both the human syndrome and the mouse model (Fmr1-/ y) may be due to delayed synaptic spine maturation and excessive arborization of somatosensory neurons (Irwin et al., 2000; Nimchinsky et al., 2001). However, there has been no investigation into the functional maturation of the primary excitatory somatosensory synapses in fragile X syndrome.;Layer IV rodent somatosensory cortex is organized into discrete barrels arranged as an isomorphic map of the whisker array on the contralateral snout. In the barrels, excitatory glutamatergic synapses between thalamic afferents and layer IV spiny stellate neurons mature over the first postnatal week. The concurrent critical period for long term plasticity at these synapses overlaps the critical period for barrel map formation and lesion induced map plasticity (Crair and Malenka, 1995; Feldman et al., 1999; Feldman et al., 1998). Thus, the mouse barrel cortex provides a unique system for studying cortical developmental disruptions in sensory integration associated with fragile X syndrome and autism.;This study follows the development of the primary sensory inputs to somatosensory cortex in mice that lack FMRP. Electrophysiological recordings from layer IV somatosensory neurons uncovered a temporal shift in the critical period for thalamocortical synaptic plasticity in Fmr1-/y mice, accompanied by delayed development of glutamateric synaptic transmission and an excess of silent, NMDA-only, synapses at the end of the classical critical period. Alterations in synaptic development did not translate into gross anatomical deficits; neither barrel map development nor the critical period for lesion induced map plasticity was affected in fragile X mice. Together, the results indicate that while FMRP is important for normal maturation of thalamocortical synapses and the window for synaptic plasticity, it is not necessary for barrel map development. Furthermore, this is the first evidence for a shift in the critical period in somatosensory cortex and may be valuable for understanding how critical periods impact cortical circuit formation and subsequent adult behavior and cognition. |
