The Journal of Neuroscience, May 1, 2002, 22(9):3692-3699
The Requirement of Presynaptic Metabotropic Glutamate Receptors
for the Maintenance of Locomotion
Michiko
Takahashi1 and
Simon
Alford2
1 Department of Physiology, Northwestern University
Medical School, Chicago, Illinois 60611, and 2 Department
of Biological Sciences, University of Illinois at Chicago, Chicago,
Illinois 60607
Spinal circuits known as central pattern generators maintain
vertebrate locomotion. In the lamprey, the contralaterally alternating ventral root activity that defines this behavior is driven by ipsilateral glutamatergic excitation (Buchanan and Grillner, 1987) coupled with crossed glycinergic inhibition (Buchanan, 1982; Alford and
Williams, 1989). These mechanisms are distributed throughout the spinal
cord. Glutamatergic excitatory synapses activate AMPA and NMDA
receptors known to be necessary for the maintenance of the locomotor
rhythm. Less is known of the role and location of metabotropic
glutamate receptors (mGluRs), although group I mGluRs enhance
transmitter release at giant synapses in the lamprey spinal cord,
whereas group II/III receptors may inhibit release. In this study we
show that group I mGluR antagonists block fictive locomotion, a neural
correlate of locomotion, by acting at the presynaptic terminal. Under
physiological conditions, synaptically released glutamate activates
presynaptic group I mGluRs (autoreceptors) during the repetitive
activation of glutamatergic terminals. The resulting rise in
[Ca2+]i caused by the release from
presynaptic intracellular stores is coincident with an enhancement of
synaptic transmission. Thus, blocking mGluRs reduces glutamate release
during the repetitive activity that is characteristic of locomotion,
leading to the arrest of locomotor activity. We found the effects of
group I mGluRs on locomotion to be inconsistent with a postsynaptic
effect on the central pattern generator. Consequently, the activation of metabotropic glutamate autoreceptors is necessary to maintain rhythmic motor output. Our results demonstrate the role of presynaptic mGluRs in the physiological control of movement for the first time.
Key words:
neurotransmitter release; fictive locomotion; glutamate; lamprey; central pattern generator; presynaptic
Copyright © 2002 Society for Neuroscience 0270-6474/02/2293692-08$05.00/0
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