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Activity-Dependent Maturation of Inhibitory Processing in the Spinal Dorsal Horn (ADMIP)
Start date: 01 Mar 2015, End date: 28 Feb 2018 PROJECT  FINISHED 

In the early postnatal period neonates are particularly sensitive to touch, often responding with exaggerated reflexes and whole-body movements to an isolated cutaneous stimulus. This suggests a predominance of excitation over inhibition in spinal sensory networks, which may facilitate activity-dependent synaptic strengthening. We have recently shown that neonatal hypersensitivity to touch is due to the late maturation of glycinergic inhibitory signalling and that this signalling, in turn, requires nociceptive activity in the dorsal horn at a critical postnatal period. However, the phenotype of the interneurons involved and the mechanism for their maturation remains to be determined. Parvalbumin expressing neurons form a subgroup of inhibitory interneurons that express both GABA and glycine and are involved in the control of innocuous afferent input in the adult dorsal horn making them a key target for this process. Our pilot data shows that parvalbumin is not expressed in the dorsal horn until the second postnatal week, coinciding with the behavioural decrease in touch-hypersensitivity. Using a combination of cutting edge targeted genetic manipulations and in vivo electrophysiological recordings of dorsal horn neurons, this project will identify which populations of interneurons inhibit tactile activity in the neonatal and adult dorsal horn and which primary afferent inputs drive their activity-dependent maturation. This data will provide fundamental biological knowledge required for better management of infants in intensive care.
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