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Peter KIND"Cortical development in mouse models of intellectual disability"

Abstract :


One issue addressed in my lab is: What are the key synaptic proteins that regulate activity-development of the cerebral cortex and how do they regulate synaptic development?




The brain develops as a result of a complex interplay between genetic instruction (Nature) and experience (Nurture). Our laboratory is interested in genes that allow the brain to learn and store information during development.
At the heart of both childhood and adult learning and memory are the molecules that regulate the way neurons communicate, namely neurotransmitter receptors and their downstream signaling pathways.
Recently several forms of childhood cognitive impairment, including Fragile X Syndrome (FXS), have been shown to result from genetic alteration of genes encoding proteins that regulate glutamate receptors signaling and synaptic development.
FXS is the most common form of genetically inherited cognitive impairment with a prevalence of approximately 1:4000 boys and 1:8000 girls.
FXS results from genetic silencing of the fragile X mental retardation gene (Fmr1), which encodes the fragile X mental retardation protein (FMRP).
FMRP is a key regulator of synaptic development and belongs to a family of “synaptopathies” caused by genetic disruption of genes that encode synaptic proteins that result in altered synaptic development.
Other synaptic proteins being examined in the laboratory whose disruption leads to cognitive impairment in humans include SynGAP and SAP-102.
Finally we are examining the role of the Tuberous Sclerosis genes (Tsc1 and Tsc2) in cortical development.

Selected publications

HarlowEG, Till SM, Russell TA, Wijetunge LS, Kind PC, Contractor A Critical period plasticity is disrupted in the barrel cortex of Fmr1 knockout mice. Neuron 65, 385-398.

Wijetunge L, Till S, Ingham C, Gillingwater T and Kind PC (2008) mGluR5 Regulates Glutamate-Dependent Development of the Mouse Somatosensory Cortex. Journal of Neuroscience 28:13028-13037.

Watson RF, Abdel-Majid RM, Barnett MW, Willis BS, Katsnelson A, Gillingwater TH, McKnight GS, Kind PC, and Neumann PE (2006) Involvement of Protein Kinase A in Patterning of the Mouse Somatosensory Cortex. Journal of Neuroscience 17:5393-5361.

Barnett MW, Watson R, Vitalis T, Porter K, Komiyama NH, Stoney PN, Gillingwater TH, Grant SGN and Kind PC (2008) SynGAP regulates pattern formation in the trigeminal system of mice. Journal of Neuroscience 26:1355-1365.

Kind PC, Mitchell DE, Ahmed B, Blakemore C, Bonhoeffer T and Sengpiel F (2002) Correlated binocular activity guides recovery from monocular deprivation. Nature 416:430-433..

Scientific focus :

The research projects in my laboratory are addressing several key issues:
What are the key synaptic proteins that regulate activity-development of the cerebral cortex and how do they regulate synaptic development?
What phenotypic alterations result from loss of these synaptic proteins and when do they first appear during development?
Can we reverse any of the altered phenotypes caused by the genetic disruption of Fmr1 and Tsc?

Valentin Nagerl de l'IINS