Modulatory effects and interactions of substance P, dopamine and 5-HT in a neuronal network
Author: Svensson, Erik
Date: 2003-05-09
Location: Hillarpsalen, Retzius väg 8
Time: 9.00
Department: Institutionen för neurovetenskap / Department of Neuroscience
Abstract
The spinal neuronal network that generates the locomotor rhythm in lamprey contains excitatory and inhibitory interneurons, reticulospinal inputs from the brainstem, and motor neurons. In this thesis, I have studied how the spinal locomotor network cart be modulated by a tachykinin, dopamine and 5- HT that are co-localized in midline neurons situated below the central canal.
* The midline neurons are rhythmically active during NMDA-induced fictive locomotion and are thus an integral part of the spinal locomotor network.
* Substance P alone induces synaptically-driven membrane potential oscillations in motor neurons. It also depolarizes the membrane potential by the reduction of a potassium conductance, and potentiates the Ca2+ current in motor neurons, while it reduces the Ca2+ current in inhibitory interneurons.
* Endogenously released dopamine has a biphasic effect on fictive locomotion, as does exogenously applied dopamine. The effect is manifested as an increase in the frequency at low dopamine concentrations followed by a decrease in frequency with higher dopamine concentrations. Endogenous and exogenous dopamine reduces the amplitude of reticulospinal glutamatergic EPSPs, via an action of D2-receptors on Ntype Ca2+ channels.
* 5-HT inhibits the N-type Ca 2+_channels via a 5-HT1A receptor coupled to a pertussis toxin sensitive G-protein. This will in turn reduce the Ca2+-dependent sAHP in spinal neurons.
* The interactions between these three modulators were investigated. 5-HT, but not dopamine, counteracted the long-lasting potentiation (>24 h) of the frequency of fictive locomotion caused by a short lasting application of substance P (10 min) that is dependent on potentiation of postsynaptic NMDA-responses. Substance P also presynaptically potentiates glutamate release, which is blocked by 5-HT, but not by dopamine. Dopamine, on the other hand, reduces the inhibitory effect of 5-HT on the substance P-induced glutamate release. Dopamine thus presynaptically promotes the effect of substance P. 5-HT can be considered a "metamodulator" of substance P, and dopamine as a metamodulator of 5-HT and a "tertiary modulator" of the 5HT/substance P interaction.
* The midline neurons are rhythmically active during NMDA-induced fictive locomotion and are thus an integral part of the spinal locomotor network.
* Substance P alone induces synaptically-driven membrane potential oscillations in motor neurons. It also depolarizes the membrane potential by the reduction of a potassium conductance, and potentiates the Ca2+ current in motor neurons, while it reduces the Ca2+ current in inhibitory interneurons.
* Endogenously released dopamine has a biphasic effect on fictive locomotion, as does exogenously applied dopamine. The effect is manifested as an increase in the frequency at low dopamine concentrations followed by a decrease in frequency with higher dopamine concentrations. Endogenous and exogenous dopamine reduces the amplitude of reticulospinal glutamatergic EPSPs, via an action of D2-receptors on Ntype Ca2+ channels.
* 5-HT inhibits the N-type Ca 2+_channels via a 5-HT1A receptor coupled to a pertussis toxin sensitive G-protein. This will in turn reduce the Ca2+-dependent sAHP in spinal neurons.
* The interactions between these three modulators were investigated. 5-HT, but not dopamine, counteracted the long-lasting potentiation (>24 h) of the frequency of fictive locomotion caused by a short lasting application of substance P (10 min) that is dependent on potentiation of postsynaptic NMDA-responses. Substance P also presynaptically potentiates glutamate release, which is blocked by 5-HT, but not by dopamine. Dopamine, on the other hand, reduces the inhibitory effect of 5-HT on the substance P-induced glutamate release. Dopamine thus presynaptically promotes the effect of substance P. 5-HT can be considered a "metamodulator" of substance P, and dopamine as a metamodulator of 5-HT and a "tertiary modulator" of the 5HT/substance P interaction.
List of papers:
I. Svensson E, Grillner S, Parker D (2002). Synaptically evoked membrane potential oscillations induced by substance P in lamprey motor neurons. J Neurophysiol. 87(1): 113-21.
Pubmed
II. Svensson E, Grillner S, Parker D (2003). Substance P differentially modulates Ca2+-conductances in identified spinal neurons in lamprey. [Manuscript]
III. Svensson E, Wikstrom MA, Hill RH, Grillner S (2003). Endogenous and exogenous dopamine presynaptically inhibits glutamatergic reticulospinal transmission via an action of D2-receptors on N-type Ca2+ channels. Eur J Neurosci. 17(3): 447-54.
Pubmed
IV. Svensson E, Woolley J, Wikstrom MA, Grillner S (2003). Endogenous dopaminergic modulation of the lamprey spinal locomotor network. Brain Research.
V. Hill RH, Svensson E, Deweal J, Grillner S (2003). 5-HT inhibits N-type but not L-type Ca2+ channels via 5-HT1A receptors in lamprey spinal neurons. [Manuscript]
VI. Svensson E, Grillner S, Hill RH (2003). Modulator-containing midline neurons are rhythmically active during fivtive locomotion in the lamprey spinal cord. [Manuscript]
VII. Svensson E, Grillner S, Parker D (2001). Gating and braking of short- and long-term modulatory effects by interactions between colocalized neuromodulators. J Neurosci. 21(16): 5984-92.
Pubmed
I. Svensson E, Grillner S, Parker D (2002). Synaptically evoked membrane potential oscillations induced by substance P in lamprey motor neurons. J Neurophysiol. 87(1): 113-21.
Pubmed
II. Svensson E, Grillner S, Parker D (2003). Substance P differentially modulates Ca2+-conductances in identified spinal neurons in lamprey. [Manuscript]
III. Svensson E, Wikstrom MA, Hill RH, Grillner S (2003). Endogenous and exogenous dopamine presynaptically inhibits glutamatergic reticulospinal transmission via an action of D2-receptors on N-type Ca2+ channels. Eur J Neurosci. 17(3): 447-54.
Pubmed
IV. Svensson E, Woolley J, Wikstrom MA, Grillner S (2003). Endogenous dopaminergic modulation of the lamprey spinal locomotor network. Brain Research.
V. Hill RH, Svensson E, Deweal J, Grillner S (2003). 5-HT inhibits N-type but not L-type Ca2+ channels via 5-HT1A receptors in lamprey spinal neurons. [Manuscript]
VI. Svensson E, Grillner S, Hill RH (2003). Modulator-containing midline neurons are rhythmically active during fivtive locomotion in the lamprey spinal cord. [Manuscript]
VII. Svensson E, Grillner S, Parker D (2001). Gating and braking of short- and long-term modulatory effects by interactions between colocalized neuromodulators. J Neurosci. 21(16): 5984-92.
Pubmed
Issue date: 2003-04-18
Publication year: 2003
ISBN: 91-7349-524-7
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