Role of excitatory amino acids in mediating burst discharge of red nucleus neurons in the in vitro turtle brain stem-cerebellum

1991 ◽  
Vol 65 (3) ◽  
pp. 454-467 ◽  
Author(s):  
J. Keifer ◽  
J. C. Houk
Keyword(s):  
Spinal Cord ◽  
Amino Acid ◽  
Nmda Receptor ◽  
Excitatory Amino Acid ◽  
Red Nucleus ◽  
Nmda Receptor Antagonist ◽  
Excitatory Amino Acid Receptor ◽  
Bath Application

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)

Excitatory amino acid receptor-mediated transmission in geniculocortical and intracortical pathways within visual cortex

1991 ◽  
Vol 66 (1) ◽  
pp. 293-306 ◽  
Author(s):  
L. J. Larson-Prior ◽  
P. S. Ulinski ◽  
N. T. Slater
Keyword(s):  
Visual Cortex ◽  
Amino Acid ◽  
Cortical Neurons ◽  
Excitatory Amino Acid ◽  
Nmda Antagonist ◽  
Receptor Subtypes ◽  
Excitatory Amino Acid Receptor ◽  
Visual Cortical ◽  
Stimulation Of

1. A preparation of turtle (Chrysemys picta and Pseudemys scripta) brain in which the integrity of the intracortical and geniculocortical pathways in visual cortex are maintained in vitro has been used to differentiate the excitatory amino acid (EAA) receptor subtypes involved in geniculocortical and intracortical synapses. 2. Stimulation of the geniculocortical fibers at subcortical loci produces monosynaptic excitatory postsynaptic potentials (EPSPs) in visual cortical neurons. These EPSPs are blocked by the broad-spectrum EAA receptor antagonist kynurenate (1-2 mM) and the non-N-methyl-D-aspartate (NMDA) antagonist 6, 7-dinitroquinoxaline-2,3-dione (DNQX, 10 microM), but not by the NMDA antagonist D,L-2-amino-5-phosphonovalerate (D,L-AP-5, 100 microM). These results indicate that the geniculocortical EPSP is mediated by EAAs that access principally, if not exclusively, EAA receptors of the non-NMDA subtypes. 3. Stimulation of intracortical fibers evokes compound EPSPs that could be resolved into three components differing in latency to peak. The component with the shortest latency was not affected by any of the EAA-receptor antagonists tested. The second component, of intermediate latency, was blocked by kyurenate and DNQX but not by D,L-AP-5. The component of longest latency was blocked by kynurenate and D,L-AP-5, but not by DNQX. These results indicate that the compound intracortical EPSP is comprised of three pharmacologically distinct components that are mediated by an unknown receptor, by quisqualate/kainate, and by NMDA receptors, respectively. 4. Repetitive stimulation of intracortical pathways at 0.33 Hz produces a dramatic potentiation of the late, D,L-AP-5-sensitive component of the intracortical EPSP. 5. These experiments lead to a hypothesis about the subtypes of EAA receptors that are accessed by the geniculocortical and intracortical pathways within visual cortex.

Effect of Pretreatment with Intrathecal Excitatory Amino Acid Receptor Antagonists on the Development of Pain Behavior Caused by Plantar Incision

2000 ◽  
Vol 93 (2) ◽  
pp. 489-496 ◽  
Author(s):  
Esther M. Pogatzki ◽  
Peter K. Zahn ◽  
Timothy J. Brennan
Keyword(s):  
Amino Acid ◽  
Nmda Receptor ◽  
Excitatory Amino Acid ◽  
Pain Behavior ◽  
Receptor Antagonists ◽  
Excitatory Amino Acid Receptor ◽  
Mk 801 ◽  
Acid Receptor ◽  
Group I ◽  
Plantar Incision

Background Drugs that block spinal excitatory amino acid receptor activation may prevent pain after surgery. The authors previously studied the effect of excitatory amino acid receptor antagonists after incision. In the present study, we examined the role of N-methyl-d-aspartate (NMDA), non-NMDA, and metabotropic glutamate receptors (mGluRs) on the development of pain behavior after plantar incision. Methods Rats with lumbar intrathecal catheters were anesthetized with halothane. Fifteen minutes before an incision was made, drug [40 nmol MK-801; 20 nmol NBQX; or 200 nmol (+)-MCPG] or vehicle was injected intrathecally followed by an infusion of the same drug for 75 min. Withdrawal thresholds to calibrated von Frey filaments applied adjacent to the wound and response frequencies to a blunt mechanical stimulus applied directly to the wound were measured before incision and 1, 2, 4, and 6 h after incision and then once daily for 6 days. Results Preincision treatments with antagonists against the NMDA (MK-801) and group I and II metabotropic receptors [(+)-MCPG] did not inhibit the development of mechanical hyperalgesia caused by incision. Preincision treatment with the non-NMDA receptor antagonist NBQX increased withdrawal thresholds at 1 and 2 h and on postoperative day 1 compared with the vehicle group; response frequencies were reduced 1 and 2 h after incision and on postoperative day 2 (P < 0.05). In an additional group, postincision treatment with NBQX was similar to preincision treatment. Conclusion Spinal NMDA and mGluR antagonists may not be useful for preventing postsurgical pain. Spinal non-NMDA receptor antagonists reduced pain behaviors, but a preventive effect using preincision treatment was not apparent.

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