Effect of metabotropic glutamate receptor activity on rhythmic discharges of the neonatal rat spinal cord in vitro.
To extend our understanding of the network-based properties which enable a neuronal circuit to produce sustained electrical oscillations, we explored the potential contribution of metabotropic glutamate receptors (mGluRs) to generation of rhythmic discharges. The in vitro spinal cord of the neonatal rat was used as a model to find out if electrical patterns characterized by either alternating or synchronous motor pool discharges (recorded from lumbar ventral roots) required mGluR activation or were modulated by it. Alternating patterns of fictive locomotion (induced by NMDA and 5HT) were slowed down and blocked by the broad spectrum mGluR agonist (+/-)-1-aminocyclopentane-trans-1, 3-dicarboxylic acid (t-ACPD; 5-50 microM) and unaffected by the broad spectrum mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG; 1 mM). The regular, synchronous bursting emerging in the presence of strychnine and bicuculline was accelerated by t-ACPD with a commensurate decrease in single burst length, an effect antagonized by MCPG which per se did not affect bursting. The action of t-ACPD was selectively inhibited by the L-type Ca2+ blocker nifedipine which, however, did not change rhythm acceleration evoked by NMDA. These data suggest that neither alternating nor synchronous oscillatory discharges were apparently dependent on mGluR activation via endogenously released glutamate. However, mGluR activation by the agonist t-ACPD modulated rhythmic patterns, indicating that such receptors are a potential target for pharmacological up- or downregulation of spinal rhythmicity.
Taccola
Giuliano
G
Biophysics Sector and INFM Unit, International School for Advanced Studies, 34014 Trieste, Italy.
Marchetti
Cristina
C
Nistri
Andrea
A
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D001683:Biological Clocks / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009415:Nerve Net / Q000166:cytology / Q000378:metabolism; D010507:Periodicity; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D012701:Serotonin; D016202:N-Methylaspartate; D013331:Strychnine; D001640:Bicuculline