Schwaller, F; (2016) What the young brain tells the spinal cord: top-down modulation of dorsal horn sensory circuitry during postnatal development. Doctoral thesis , UCL (University College London).

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Abstract

The brain can endogenously and powerfully modulate the processing of somatosensory information in the spinal cord. In adults, the rostroventral medulla (RVM) can inhibit and facilitate somatosensory processing in the adult dorsal horn, providing powerful control of pain behaviours. In neonates, balanced descending control of processing of dorsal horn activity is immature. Here, I examine the anatomical and functional maturation of descending control of spinal sensory circuitry in rats and hypothesise that descending serotonergic neurons in the RVM provide ongoing descending facilitation of spinal sensory networks in young animals. In chapter 2, I demonstrate that cutaneous noxious stimulation activates neurons in regions of the brainstem which receive sensory inputs from the dorsal horn at P4; eight days before noxious-evoked neuronal activation in descending modulatory nuclei. In chapter 3, silencing the RVM unmasked descending facilitation of nociceptive dorsal horn neuron electrophysiological activity in uninjured P8 and P21 rats, but unmasked descending facilitation at P40. Thus, there is a switch from ongoing descending facilitation to inhibition between P21 and P40. Experiments in chapter 4 demonstrate anatomical maturation of descending serotonergic pathways from the RVM to the spinal cord during postnatal development. In chapter 5, the function of these pathways was investigated. Here, deletion of descending serotonergic fibres or blockade of spinal 5-HT3Rs unmasked background serotonergic facilitation of tactile and noxious dorsal horn neuron electrophysiological activity at P8 and P21. In adults, 5-HT/5-HT3Rs also facilitate tactile inputs in the dorsal horn, but net modulation of noxious inputs switches to be inhibitory. In conclusion, a change in function of descending modulatory pathways arising from the brainstem occurs during postnatal development: in young rats, descending modulatory pathways enhance the saliency of low and high threshold mechanical inputs in the dorsal horn, whilst balanced inhibition and excitation of high and low threshold inputs occurs in adulthood.

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