Koch, S.C.; (2010) The developmental regulation of local and descending control of dorsal horn neurons in the rat. Doctoral thesis , UCL (University College London).

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Abstract

Neonatal responses to peripheral cutaneous sensory stimuli appear hyperexcitable compared to those of the adult, at both behavioural and cellular levels. Little is known, however, of the mechanisms involved in the maturation of this sensory circuitry over the postnatal period. I hypothesise that the excitability of neonatal networks is due to immature local and descending inhibitory control of spinal circuits. To test this I have examined the maturation of descending and local inhibitory spinal circuitry using immunohistochemical staining in the dorsal horn, in vivo electrophysiological recordings of dorsal horn neurons and stimulation of brainstem descending pathways. Firstly, I mapped the development of spinal glycinergic circuitry over the first three postnatal weeks using immunohistochemical staining of glycinergic terminals and receptors. Results show a clear shift in expression pattern from deep dorsal horn staining of both glycinergic terminals and receptors in the neonate, to selective expression in lamina III by the third postnatal week. I then characterised the functional development of glycinergic inhibition of spinal sensory pathways at a cellular level using in vivo extracellular recordings of dorsal horn neurons in neonatal and adolescent rats in the presence of the glycine receptor antagonist strychnine. Results illustrate an absence of glycinergic inhibition of sensory stimuli until postnatal day 21 and a facilitatory role of glycine in the transmission of low-threshold stimuli in the neonatal spinal cord. Finally, I examined the descending influence of the rostroventral medulla on dorsal horn neuronal activity over postnatal development. Results indicate that the influence of descending control shifts dramatically from predominantly excitatory in early development, to predominantly inhibitory at a later stage in life. In conclusion, there is significant postnatal modulation of segmental and descending influences on spinal networks in the postnatal period, both of which are likely to contribute to the maturation of cutaneous sensory spinal processing.

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