Glutamate Receptor Antagonists Block Gustatory Afferent Input to the Nucleus of the Solitary Tract

1997 ◽  
Vol 77 (3) ◽  
pp. 1514-1525 ◽  
Author(s):  
Cheng-Shu Li ◽  
David V. Smith
Keyword(s):  
Receptor Antagonist ◽  
Glutamate Receptor ◽  
Drug Administration ◽  
Afferent Input ◽  
Chemical Stimulation ◽  
Kainate Receptor ◽  
Solitary Tract ◽  
Receptor Antagonists ◽  
Glutamate Receptor Antagonists ◽  
Stimulation Of

Li, Cheng-Shu and David V. Smith. Glutamate receptor antagonists block gustatory afferent input to the nucleus of the solitary tract. J. Neurophysiol. 77: 1514–1525, 1997. The effects of excitatory amino acid (EAA) receptor antagonists in blocking the synaptic transmission between gustatory fibers of the chorda tympani (CT) nerve and taste-responsive neurons within the nucleus of the solitary tract (NST) were examined electrophysiologically in urethan-anesthetized hamsters. Single neurons in the NST were recorded extracellularly and drugs were microinjected into the vicinity of the cell with the use of a multibarrel pipette assembly. The activity of each cell was recorded in response to lingual stimulation with 0.032 M NaCl, 0.032 M sucrose, 0.0032 M citric acid, 0.032 M quinine hydrochloride, and/or 25-μA anodal current pulses. Once a cell was identified as a taste-responsive neuron, one or more EAA receptor antagonists were administered by microinjection. Approximately 27 nl of 50 mM kynurenic acid (KYN), a broad-spectrum EAA receptor antagonist; 0.5 or 2.0 mM dl-2-amino-5-phosphonovalerate (APV), an N-methyl-d-aspartate (NMDA) receptor antagonist; 0.05 or 0.5 mM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist; or phosphate-buffered physiological saline was applied to the neuron. Responses to chemical stimulation of the anterior tongue were obtained before and after drug administration and again after recovery; responses to anodal current stimulation (0.1 Hz) were obtained continually throughout the drug administration protocol. Microinjection of KYN completely and reversibly abolished responses elicited by both anodal current and chemical stimulation of the anterior tongue. The excitatory responses of cells in the NST to chemical and electrical stimulation of the anterior tongue were also completely and reversibly blocked by CNQX, implicating the involvement of an AMPA/kainate receptor. Microinjection of APV was generally less effective and partially reduced the responses of some taste-responsive NST cells to chemical stimulation of the anterior tongue. There were no effects following microinjection of a 27-nl bolus of phosphate-buffered saline. None of these EAA receptor antagonists had a differential effect on responses to different taste stimuli. The responses to all tastants were completely blocked by both KYN and CNQX; there was no apparent relationship between the response to any particular tastant and the limited effects of APV. These data implicate glutamate as an excitatory neurotransmitter between CT gustatory fibers and taste-responsive NST cells and suggest that it acts primarily on AMPA/kainate receptors, with some contribution from NMDA receptors. This conclusion is strengthened by other data obtained from in vitro slice preparations, which show that responses of cells in the rostral NST to solitary tract stimulation are blocked by both NMDA and AMPA/kainate receptor antagonists.

Analgesic Interaction between Intrathecal Midazolam and Glutamate Receptor Antagonists on Thermal-induced Pain in Rats 

1999 ◽  
Vol 91 (2) ◽  
pp. 531-537 ◽  
Author(s):  
Tomoki Nishiyama ◽  
Laszlo Gyermek ◽  
Chingmuh Lee ◽  
Sachiko Kawasaki-Yatsugi ◽  
Tokio Yamaguchi
Keyword(s):  
Receptor Antagonist ◽  
Glutamate Receptor ◽  
Ampa Receptor ◽  
Behavioral Changes ◽  
Tail Flick ◽  
Receptor Antagonists ◽  
Thermal Nociception ◽  
Motor Disturbance ◽  
Ampa Receptor Antagonist ◽  
Glutamate Receptor Antagonists

Background Two major neurotransmitters, gamma-aminobutyric acid (GABA) and the excitatory amino acid, glutamate, may be involved in nociception in the spinal cord. GABA and glutamate receptors may operate in concert to modify signals in the central nervous system. The purpose of this study was to investigate the spinal analgesic interaction between midazolam, a benzodiazepine-GABA(A) receptor agonist, and two glutamate receptor antagonists on acute thermal nociception. Methods Sprague-Dawley rats were implanted with chronic lumbar intrathecal catheters and were tested for their tail withdrawal response by the tail flick test after intrathecal administration of saline, midazolam (1-100 microg), AP-5 (1-30 microg), or YM872 (0.3-30 microg). AP-5 is an N-methyl-D-aspartate (NMDA) receptor antagonist and YM872 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist. The combination of midazolam and the other two agents were also tested by isobolographic analyses. Motor disturbance and behavioral changes were observed. Results Dose-dependent increases in the tail flick latency were observed with midazolam, AP-5, and YM872 with 50% effective dose values of 1.57+/-0.34 (SEM) microg, 5.54+/-0.19 microg, and 1.0+/-0.22 microg, respectively. A potent synergy in analgesia with decreased behavioral changes and motor disturbance was obtained when combining midazolam with AP-5 or YM872. Conclusions Spinally administered midazolam and an NMDA- or an AMPA-receptor antagonist exhibited potent synergistic analgesia on acute thermal nociception in rats. Side effects, shown by behavioral changes and motor disturbance, decreased with the combination of the agents. These results point out an important direction for the study of acute nociception.

Commissural and Lemniscal Synaptic Input to the Gerbil Inferior Colliculus

1998 ◽  
Vol 80 (5) ◽  
pp. 2229-2236 ◽  
Author(s):  
David R. Moore ◽  
Vibhakar C. Kotak ◽  
Dan H. Sanes
Keyword(s):  
Inferior Colliculus ◽  
Glutamate Receptor ◽  
Synaptic Input ◽  
Inhibitory Input ◽  
Ionotropic Glutamate Receptor ◽  
Receptor Antagonists ◽  
Synaptic Currents ◽  
Glutamate Receptor Antagonists ◽  
Stimulation Of ◽  
Synaptic Responses

Moore, David R., Vibhakar C. Kotak, and Dan H. Sanes. Commissural and lemniscal synaptic input to the gerbil inferior colliculus. J. Neurophysiol. 80: 2229–2236, 1998. The central nucleus of the inferior colliculus (ICC) receives direct inputs, bilaterally, from all auditory brain stem nuclear groups. To evaluate the contribution made to gerbil ICC neuron physiology by two major afferent pathways, we examined the synaptic responses evoked by direct stimulation of the commissure of the inferior colliculus (CIC) and the ipsilateral lateral lemniscus (LL). Frontal midbrain slices were obtained from postnatal day (P) 9–P19 gerbils, and whole cell recordings were made under current- ( n = 22) or voltage-clamp ( n = 52) conditions. Excitatory and inhibitory synaptic responses were characterized by sequentially exposing the slice to ionotropic glutamate receptor antagonists [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) + aminophosphonpentanoic acid (AP-5), or kynurenic acid)], a γ-aminobutryic acid type A receptor antagonist (bicuculline), and a glycine receptor antagonist (strychnine). In current clamp, LL stimulation typically produced a short latency depolarization followed by a longer duration hyperpolarization. The depolarization was abolished by AP-5 + CNQX, and the remaining inhibitory potential displayed either bicuculline or strychnine sensitivity. In voltage clamp, 79% of ICC neurons displayed synaptic currents after stimulation of each pathway. The synaptic currents were typically complex waveforms, and ionotropic glutamate receptor antagonists reduced inward currents at a holding potential of −80 mV in the majority of neurons. In addition, this treatment reduced outward synaptic currents at a holding potential of −20 mV, indicating that inhibitory interneuronal input was often activated by LL or CIC afferents. A minority of neurons had synaptic currents that were unaffected by glutamate receptor antagonists, but it was more common for CIC-evoked currents to be unaffected (38%) rather than LL-evoked currents (22%). The CIC provided a strong inhibitory input that was almost exclusively GABAergic, whereas the LL inhibition often included a glycinergic component. These experiments have shown that the CIC provides a major glutamatergic and GABAergic input to most ICC neurons. However, much of the inhibitory input from both the CIC and the LL appears to be mediated by interneuronal connections.

The Analgesic Interaction Between Intrathecal Clonidine and Glutamate Receptor Antagonists on Thermal and Formalin-Induced Pain in Rats

2001 ◽  
pp. 725-732 ◽  
Author(s):  
Tomoki Nishiyama ◽  
Laszlo Gyermek ◽  
Chingmuh Lee ◽  
Sachiko Kawasaki-Yatsugi ◽  
Tokio Yamaguchi ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Receptor Antagonists ◽  
Glutamate Receptor Antagonists ◽  
Intrathecal Clonidine

Synaptic Responses of Neurons Controlling the Parotid and von Ebner Salivary Glands in Rats to Stimulation of the Solitary Nucleus and Tract

2008 ◽  
Vol 99 (3) ◽  
pp. 1267-1273 ◽  
Author(s):  
Takeshi Suwabe ◽  
Hideyuki Fukami ◽  
Robert M. Bradley
Keyword(s):  
Salivary Glands ◽  
Sensory Information ◽  
Salivary Secretion ◽  
Afferent Input ◽  
Membrane Hyperpolarization ◽  
Neuron Response ◽  
Glutamate Receptor Antagonists ◽  
Autonomic Neurons ◽  
Reflex Stimulation ◽  
Stimulation Of

Salivary secretion results from reflex stimulation of autonomic neurons via afferent sensory information relayed to neurons in the rostral nucleus of the solitary tract (rNST), which synapse with autonomic neurons of the salivatory nuclei. We investigated the synaptic properties of the afferent sensory connection to neurons in the inferior salivatory nucleus (ISN) controlling the parotid and von Ebner salivary glands. Mean synaptic latency recorded from parotid gland neurons was significantly shorter than von Ebner gland neurons. Superfusion of GABA and glycine resulted in a concentration-dependent membrane hyperpolarization. Use of glutamate receptor antagonists indicated that both AMPA and N-methyl-d-aspartate (NMDA) receptors are involved in the evoked excitatory postsynaptic potentials (EPSPs). Inhibitory postsynaptic potential (IPSP) amplitude increased with higher intensity ST stimulation. Addition of the glycine antagonist strychnine did not affect the amplitude of the IPSPs significantly. The GABAA receptor antagonist, bicuculline (BMI) or mixture of strychnine and BMI abolished the IPSPs in all neurons. IPSP latency was longer than EPSP latency, suggesting that more than one synapse is involved in the inhibitory pathway. Results show that ISN neurons receive both excitatory and inhibitory afferent input mediated by glutamate and GABA respectively. The ISN neuron response to glycine probably derives from descending connections. Difference in the synaptic characteristics of ISN neurons controlling the parotid and von Ebner glands may relate to the different function of these two glands.

Imaging Anoxic Depolarization During Ischemia-Like Conditions in the Mouse Hemi-Brain Slice

2001 ◽  
Vol 85 (1) ◽  
pp. 414-424 ◽  
Author(s):  
I. Joshi ◽  
R. D. Andrew
Keyword(s):  
Glutamate Receptor ◽  
Brain Slice ◽  
Neuronal Damage ◽  
Glucose Deprivation ◽  
Light Transmittance ◽  
Cell Swelling ◽  
Receptor Antagonists ◽  
Anoxic Depolarization ◽  
Glutamate Receptor Antagonists ◽  
Ischemic Core

Focal ischemia evokes a sudden loss of membrane potential in neurons and glia of the ischemic core termed the anoxic depolarization (AD). In metabolically compromised regions with partial blood flow, peri-infarct depolarizations (PIDs) further drain energy reserves, promoting acute and delayed neuronal damage. Visualizing and quantifying the AD and PIDs and their acute deleterious effects are difficult in the intact animal. In the present study, we imaged intrinsic optical signals to measure changes in light transmittance in the mouse coronal hemi-brain slice during AD generation. The AD was induced by oxygen/glucose deprivation (OGD) or by ouabain exposure. Potential neuroprotective strategies using glutamate receptor antagonists or reduced temperature were tested. Eight minutes of OGD ( n = 18 slices) or 4 min of 100 μM ouabain ( n = 14) induced a focal increase of increased light transmittance (LT) in neocortical layers II/III that expanded concentrically to form a wave front coursing through neocortex and independently through striatum. The front was coincident with a negative voltage shift in extracellular potential. Wherever the LT front (denoting cell swelling) propagated, a decrease in LT (denoting dendritic beading) followed in its wake. In addition the evoked field potential was permanently lost, indicating neuronal damage. Glutamate receptor antagonists did not block the onset and propagation of AD or the extent of irreversible damage post-AD. Lowering temperature to 25–30°C protected the tissue from OGD damage by inhibiting AD onset. This study shows that anoxic depolarization evoked by global ischemia-like conditions is a spreading process that is focally initiated at multiple sites in cortical and subcortical gray. The combined energy demands of O2/glucose deprivation and the AD greatly exacerbate neuronal damage. Glutamate receptor antagonists neither block the AD in the ischemic core nor, we propose, block recurrent PID arising close to the core.

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