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The Journal of Neuroscience, March 1, 2002, 22(5):1868-1873

Signaling Mechanisms of Metabotropic Glutamate Receptor 5 Subtype and Its Endogenous Role in a Locomotor Network

Petronella Kettunen, Patrik Krieger, Dietmar Hess, and Abdeljabbar El Manira

Nobel Institute for Neurophysiology, Department of Neuroscience, Retzius Laboratory, Karolinska Institutet, S-171 77 Stockholm, Sweden

Metabotropic glutamate receptors (mGluRs) act as modulators in the CNS of vertebrates, but their role in motor pattern generation in particular is primarily unknown. The intracellular signaling mechanisms of the group I mGluRs (mGluR1 and mGluR5), and their endogenous role in regulating locomotor pattern generation have been investigated in the spinal cord of the lamprey. Application of the group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) produced oscillations of the intracellular Ca²⁺ concentration ([Ca²⁺]_i) in neurons. The oscillations were blocked by the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) but not by the mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester. These [Ca²⁺]_i oscillations were abolished by a phospholipase C blocker and after depletion of internal Ca²⁺ stores by thapsigargin but did not involve protein kinase C activation. Furthermore, they were dependent on Ca²⁺ influx, because no [Ca²⁺]_i oscillations were produced by DHPG in a Ca²⁺-free solution or after blockade of L-type Ca²⁺ channels. The mGluR5 is activated by an endogenous release of glutamate during locomotion, and a receptor blockade by MPEP caused an increase in the burst frequency. Thus, our results show that mGluR5 induces [Ca²⁺]_i oscillations and regulates the activity of locomotor networks through endogenous activation.

Key words: mGluR5; locomotion; spinal cord; modulation; glutamate; lamprey

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Copyright © 2002 Society for Neuroscience  0270-6474/02/2251868-06$05.00/0

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