TY - JOUR
T1 - Experience-Dependent Retinogeniculate Synapse Remodeling Is Abnormal in MeCP2-Deficient Mice
AU - Noutel, Joao
AU - Hong, Y. Kate
AU - Leu, Byunghee
AU - Kang, Erin
AU - Chen, Chinfei
N1 - Funding Information:
This work was supported by NIH R21HD058196, RO1NS070300, and PO1HD18655. J.N. was supported by funding from the Fundacao para a Ciencia e Tecnologia, Portugal. We thank the members of the Chen Laboratory, M.E. Greenberg, M. Fagiolini, and S. Cohen for helpful discussion and comments.
PY - 2011/4/14
Y1 - 2011/4/14
N2 - Mutations in MECP2 underlie the neurodevelopmental disorder Rett syndrome (RTT). One hallmark of RTT is relatively normal development followed by a later onset of symptoms. Growing evidence suggests an etiology of disrupted synaptic function, yet it is unclear how these abnormalities explain the clinical presentation of RTT. Here we investigate synapse maturation in Mecp2-deficient mice at a circuit with distinct developmental phases: the retinogeniculate synapse. We find that synapse development in mutants is comparable to that of wild-type littermates between postnatal days 9 and 21, indicating that initial phases of synapse formation, elimination, and strengthening are not significantly affected by MeCP2 absence. However, during the subsequent experience-dependent phase of synapse remodeling, the circuit becomes abnormal in mutants as retinal innervation of relay neurons increases and retinal inputs fail to strengthen further. Moreover, synaptic plasticity in response to visual deprivation is disrupted in mutants. These results suggest a crucial role for Mecp2 in experience-dependent refinement of synaptic circuits.
AB - Mutations in MECP2 underlie the neurodevelopmental disorder Rett syndrome (RTT). One hallmark of RTT is relatively normal development followed by a later onset of symptoms. Growing evidence suggests an etiology of disrupted synaptic function, yet it is unclear how these abnormalities explain the clinical presentation of RTT. Here we investigate synapse maturation in Mecp2-deficient mice at a circuit with distinct developmental phases: the retinogeniculate synapse. We find that synapse development in mutants is comparable to that of wild-type littermates between postnatal days 9 and 21, indicating that initial phases of synapse formation, elimination, and strengthening are not significantly affected by MeCP2 absence. However, during the subsequent experience-dependent phase of synapse remodeling, the circuit becomes abnormal in mutants as retinal innervation of relay neurons increases and retinal inputs fail to strengthen further. Moreover, synaptic plasticity in response to visual deprivation is disrupted in mutants. These results suggest a crucial role for Mecp2 in experience-dependent refinement of synaptic circuits.
UR - http://www.scopus.com/inward/record.url?scp=79953777487&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2011.03.001
DO - 10.1016/j.neuron.2011.03.001
M3 - Article
C2 - 21482354
AN - SCOPUS:79953777487
SN - 0896-6273
VL - 70
SP - 35
EP - 42
JO - Neuron
JF - Neuron
IS - 1
ER -