Projects per year
Abstract
Genetic mutations known to cause intellectual disabilities (ID) are concentrated in specific sets of genes including both those encoding synaptic proteins and those expressed during early development. We have characterised the effect of genetic deletion of Dlg3, an ID-related gene encoding the synaptic NMDA-receptor interacting protein SAP102, on development of the mouse somatosensory cortex. SAP102 is the main representative of the PSD-95 family of postsynaptic MAGUK proteins during early development and is proposed to play a role in stabilising receptors at immature synapses. Genetic deletion of SAP102 caused a reduction in the total number of thalamocortical (TC) axons innervating the somatosensory cortex, but did not affect the segregation of barrels. On a synaptic level SAP102 knockout mice display a transient speeding of NMDA receptor kinetics during the critical period for TC plasticity, despite no reduction in GluN2B-mediated component of synaptic transmission. These data indicated an interesting dissociation between receptor kinetics and NMDA subunit expression. Following the critical period NMDA receptor function was unaffected by loss of SAP102 but there was a reduction in the divergence of TC connectivity. These data suggest that changes in synaptic function early in development caused by mutations in SAP102 result in changes in network connectivity later in life.
Original language | English |
---|---|
Journal | Human Molecular Genetics |
Early online date | 27 Jul 2016 |
DOIs | |
Publication status | E-pub ahead of print - 27 Jul 2016 |
Fingerprint
Dive into the research topics of 'Altered Thalamocortical Development in the SAP102 Knockout Model of Intellectual Disability'. Together they form a unique fingerprint.Projects
- 2 Finished
-
The neuropathophysiology associated with Syngap mutations: further evidence for an mGluR5 signaling axis in ID/ASD
Kind, P. (Principal Investigator), Daw, M. (Co-investigator) & Wyllie, D. (Co-investigator)
1/03/13 → 31/08/16
Project: Research
-
Fragile X syndrome in development of the somatosensory cortex (Career Development Award)
Daw, M. (Principal Investigator)
1/01/09 → 30/06/15
Project: Research
Profiles
-
Michael Daw
- Deanery of Biomedical Sciences - Senior Lecturer
- Centre for Discovery Brain Sciences
- Edinburgh Neuroscience
Person: Academic: Research Active
-
Peter Kind
- Deanery of Biomedical Sciences - Personal Chair of Developmental Neuroscience
- Centre for Discovery Brain Sciences
- Edinburgh Neuroscience
Person: Academic: Research Active