Nitric Oxide signalling and the modulation of mammalian spinal motor networks (360G-Wellcome-091177_Z_10_Z)

The mammalian spinal cord contains all the neural machinery required to generate locomotor activity, even in the absence of descending and sensory input. Neuromodulation is an important component of this system, allowing locomotor activity to be modulated to suit different states or behaviours. Nitric Oxide (NO) is a potentially critical neuromodulator, about which almost nothing is known in the context of mammalian locomotion. We therefore aim to elucidate the role of NO in the control of mamma lian locomotion. We will initially determine the neuronal sources of NO in the mouse spinal cord using NADPH-d histochemistry and nNOS immunohistochemistry to reveal nitric oxide synthase expression, and DAF-2DA labelling to reveal NO production. Next, using electroneurographic recordings from ventral roots and whole-cell patch-clamp recordings from neurons in spinal cord preparations which can elicit locomotor activity, we will examine the effects of NO-mediated signalling on locomotor networks and determine underlying cellular and synaptic mechanisms. Patch-clamp analyses will concentrate on nitrergic neurons, revealed by DAF-2DA labelling, and motoneurons, the output cells of motor systems. Data obtained will address an important gap in our knowledge of spinal motor networks and provide novel information regarding NO-mediated signalling which should be applicable to other neuronal systems.