The roles of dopamine and the sodium pump in the spinal control of locomotion

Neurotransmitters;Spinal cord;Dopamine--Physiological effect;Sodium/potassium ATPase;Locomotion--Regulation

Picton, Laurence ; Sillar, Keith T. (Keith Thomas) ; Sillar, Keith T. (Keith Thomas)

University:University of St Andrews

Department:Psychology & Neuroscience (School of)

关键词: Neurotransmitters;    Spinal cord;    Dopamine--Physiological effect;    Sodium/potassium ATPase;    Locomotion--Regulation;   

Others  :  https://research-repository.st-andrews.ac.uk/bitstream/handle/10023/11359/LaurencePictonPhDThesis.pdf?sequence=2&isAllowed=y

来源: DR-NTU

【 摘 要 】

Rhythmically active, locomotor networks of the spinal cord are subject to bothneuromodulation and activity-dependent homeostatic regulation. I first show that theneuromodulator dopamine exerts potent inhibitory effects on the central pattern generator(CPG) circuit controlling locomotory swimming in post-embryonic Xenopus tadpoles.Dopamine, acting endogenously on spinal D2-like receptors, reduces spontaneous fictiveswimming occurrence and shortens, slows and weakens swimming. The mechanism involvesa TTX-resistant hyperpolarisation of rhythmically active CPG neurons, mediated by the directopening of a K+ channel with GIRK-like pharmacology. This increases rheobase and reducesspike probability.I next explore how sodium pumps contribute to the activity-dependent regulation of theXenopus swim circuit, and possible interactions of the pumps with modulators, temperatureand ionic conductances. I characterise the pump-mediated ultra-slow afterhyperpolarisation(usAHP), and show that monensin, a sodium ionophore, enhances pump activity, convertingthe usAHP into a tonic hyperpolarisation; this decreases swim episode duration and cyclefrequency. I also characterise a ZD7288-sensitive Ih current, which is active in excitatory dINinterneurons and contributes to spiking. Blocking Ih with ZD7288 decreases swim episodeduration and destabilises swim bursts. Both Ih and the usAHP increase with temperature,which depolarises CPG neurons, decreases input resistance, and increases spike probability;this increases cycle frequency, but the enhanced usAHP shortens swimming. I also show thatthe usAHP is diminished by nitric oxide, but enhanced by dopaminergic signalling.Finally, I explore sodium pumps in the neonatal mouse. The sodium pump blocker ouabainincreases the duration and frequency of drug- and sensory-induced locomotion, whilstmonensin has opposite effects. Decreasing inter-episode interval also shortens and slowsactivity, a relationship abolished by ouabain, implicating sodium pumps in a feedforward motormemory mechanism. Finally, I show that the effects of ouabain on locomotion are dependenton dopamine, which enhances a TTX- and ouabain-sensitive usAHP in spinal neurons.