Role of excitatory amino acids in mediating burst discharge of red nucleus neurons in the in vitro turtle brain stem-cerebellum.
1. Bursts of discharge have been recorded in the red nucleus in several species and are thought to represent the expression of motor commands. A cerebellorubral circuit comprised of recurrent connections among the cerebellum, red nucleus, and reticular formation was postulated to function as a positive feedback loop that generates these motor commands and transmits them to the spinal cord via the rubrospinal pathway. We have used an in vitro preparation from the turtle that leaves the circuitry connecting the cerebellum, brain stem, and spinal cord intact to study the role of excitatory amino acid neurotransmitters and recurrent excitation in mediating the generation of burst discharges in the red nucleus. 2. Burst discharges were recorded extracellularly from single cells in the red nucleus in response to single pulse or brief train stimulation of the contralateral spinal cord or brief train stimuli applied to the ipsilateral cerebellar cortex. The firing characteristics and pharmacologic sensitivities of the bursts were independent of the type of stimulus used. The bursts had long durations ranging from 2 to 17 s and showed spike frequency adaptation. 3. Transection of the cerebellar peduncle, which eliminates inhibition impinging onto the cerebellorubral circuit, greatly enhanced the spontaneous activity and burst discharges recorded in the contralateral red nucleus. Furthermore, bath application of a solution containing elevated levels of calcium and magnesium blocked the expression of burst discharges even though synaptic activation of the neurons was not blocked. 4. The possibility that excitatory amino acid receptors mediate burst responses in the red nucleus was investigated in light of the antagonistic effects of elevated magnesium ions on bursting. Bath application of 100 microns DL-2-amino-5-phosphonovaleric acid (APV), a specific N-methyl-D-aspartate (NMDA) receptor antagonist; [10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)], a specific non-NMDA receptor antagonist; or 100 microM, DL-2-amino-4-phosphonobutyric acid (AP4), an agonist of a fourth class of excitatory amino acid receptor, blocked burst activity in the red nucleus. With a multibarreled pipette for simultaneous ejection of drug and recording, iontophoresis of APV or CNQX into the red nucleus blocked bursting whereas AP4 failed to show a significant effect. These data suggest that red nucleus neurons have both NMDA and non-NMDA receptors. The site of action of the AP4-sensitive receptor appears to be elsewhere in the cerebellorubral circuit. 5. Iontophoretic application of excitatory amino acid receptor agonists NMDA and quisqualate (Q) induced excitation of red nucleus neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
Keifer
J
J
Department of Physiology, Northwestern University Medical School, Chicago, Illinois 60611.
Houk
J C
JC
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007478:Iontophoresis; D008274:Magnesium / Q000494:pharmacology; D008839:Microelectrodes; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D012012:Red Nucleus / Q000166:cytology / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014426:Turtles / Q000502:physiology*
D000596:Amino Acids; D011810:Quinoxalines; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D008274:Magnesium; D002118:Calcium