Abstract
Dopamine plays important roles in the development and modulation of motor control circuits. Here we show that dopamine exerts potent effects on the central pattern generator circuit controlling locomotory swimming in post-embryonic Xenopus tadpoles. Dopamine (0.5–100 μM) reduced fictive swim bout occurrence and caused both spontaneous and evoked episodes to become shorter, slower and weaker. The D2-like receptor agonist quinpirole mimicked this repertoire of inhibitory effects on swimming, whilst the D4 receptor antagonist, L745,870, had the opposite effects. The dopamine reuptake inhibitor bupropion potently inhibited fictive swimming, demonstrating that dopamine constitutes an endogenous modulatory system. Both dopamine and quinpirole also inhibited swimming in spinalised preparations, suggesting spinally located dopamine receptors. Dopamine and quinpirole hyperpolarised identified rhythmically active spinal neurons, increased rheobase and reduced spike probability both during swimming and in response to current injection. The hyperpolarisation was TTX-resistant and was accompanied by decreased input resistance, suggesting that dopamine opens a K+ channel. The K+ channel blocker barium chloride (but not TEA, glybenclamide or tertiapin-Q) significantly occluded the hyperpolarisation. Overall, we show that endogenously released dopamine acts upon spinally located D2-like receptors, leading to a rapid inhibitory modulation of swimming via the opening of a K+ channel.
Highlights
Neural circuits of the spinal cord that generate rhythmic locomotor activity, so called central pattern generators (CPGs), are subject to profound modulatory influences which alter neuronal properties and synaptic strengths to confer flexibility on locomotor output and behaviour[1]
The majority of neuromodulators function via changes in intracellular 2nd messenger concentrations following activation of G protein coupled receptors (GPCRs) and many neuromodulators exert their influences by activation of more than one pharmacologically distinct subset of GPCRs with distinct physiological actions
In the present study we have examined the role of dopamine at earlier stages of Xenopus development, around the time of hatching, when the animal possesses a simpler and much better defined spinal locomotor circuit[12]
Summary
Neural circuits of the spinal cord that generate rhythmic locomotor activity, so called central pattern generators (CPGs), are subject to profound modulatory influences which alter neuronal properties and synaptic strengths to confer flexibility on locomotor output and behaviour[1]. For example, acts upon two principal classes of receptor which generally exert inhibitory (D2-like: D2,D3,D4) or excitatory (D1-like: D1,D5) influences on neural circuits[3]. Effects on swimming: low dopamine concentrations activate high affinity D2-like receptors to inhibit spontaneous locomotor activity; while high dopamine concentrations facilitate locomotion by activating lower affinity D1-like receptors[6]. This previous research on older, pre-metamorphic free swimming stages of tadpole development was obtained using extracellular ventral root recordings and did not address the cellular mechanisms responsible for dopamine’s actions in the spinal cord or the developmental onset of the dopaminergic system. The mechanism appears to involve the endogenous activation of spinally located D2-like receptors, which leads to the hyperpolarisation of rhythm-generating neurons of the swim CPG via the opening of a K+ channel
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