The Barrel Cortex Model of Cortical Function and Development
The Barrel Cortex Model of Cortical Function and Development The thalamocortical (TC) input to the rodent barrel cortex is a relay for sensory information from the whiskers. This information is processed in the cortex to allow the animal to perceive shape, location and even texture of objects contacted by the whiskers.
We take advantage of the unique features of this system to study the cellular and synaptic events which underlie cortical development. Single and double patch-clamp recordings are made from cortical cells in the in vitro TC slice preparation. We use these recordings to study how the cortex processes sensory input and also to study forms of synaptic plasticity thought to underlie the sensory-dependent development of this system.
In particular we are interested in how network activity affects the induction of synaptic plasticity and how the activity of inhibitory interneurons shapes the sensory input in the cortex.
The cortex contains multiple classes of inhibitory interneuron each serving specialised functions such that identification of recorded interneurons is necessary to fully understand the roles of these cells.To this end cells are filled with biocytin during whole-cell recordings for subsequent morphological categorisation and mRNA expression profiles are established using single-cell rtPCR.
Cortical Development in Fragile-X-Syndrome
Together with Peter Kind we are using the information gained about normal development and function to identify abnormalities in a model of fragile-X-syndrome (FXS). FXS is the commonest geneticically-inherited cause of mental retardation and sufferers show impaired development of cognitive abilities associated with cortical processing. We hope that identifying developmental defects on a cellular level will lead to treatments which will stop the progression of FXS.
Daw MI., Pelkey KA., Chittajallu R., McBain CJ. (2010) Presynaptic kainate receptor activation preserves asynchronous GABA release despite the reduction in synchronous release from hippocampal cholecystokinin interneurons. J. Neurosci., 30 (33) : 11202-9.
Daw MI., Tricoire L., Erdelyi F., Szabo G., McBain CJ. (2009) Asynchronous transmitter release from cholecystokinin-containing inhibitory interneurons is widespread and target-cell independent. J. Neurosci., 29 (36) : 11112-22.
Daw MI., Ashby MC., Isaac JT. (2007) Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex. Nat. Neurosci., 10 (4) : 453-61.
Daw MI., Scott HL., Isaac JT. (2007) Developmental synaptic plasticity at the thalamocortical input to barrel cortex: mechanisms and roles. Mol. Cell. Neurosci., 34 (4): 493-502.
Daw MI., Bannister NV., Isaac JT. (2006) Rapid, activity-dependent plasticity in timing precision in neonatal barrel cortex. J. Neurosci., 26 (16) : 4178-87.
Daw MI., Bortolotto ZA., Saulle E., Zaman S., Collingridge GL., Isaac JT. (2002) Phosphatidylinositol 3 kinase regulates synapse specificity of hippocampal long-term depression. Nat. Neurosci., 5 (9) : 835-6.