scholarly journals Hitting The Right Spot: NMDA Receptors in the Auditory Thalamus May Hold the Key to Understanding Schizophrenia

2020 ◽  
Vol 23 (9) ◽  
pp. 578-580 ◽  
Author(s):  
Gang Xiao ◽  
Daniel A Llano
Keyword(s):  
Steady State ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Cortical Response ◽  
Auditory Thalamus ◽  
State Response ◽  
Nmda Receptor Blockade ◽  
Cortical Regions ◽  
The Right ◽  
Systemic Application

Abstract In this issue, Wang and colleagues solve an important puzzle in the understanding of schizophrenia. Previous work has linked N-methyl-D-aspartate (NMDA) receptor hypofunction to schizophrenia and shown that individuals with schizophrenia have a suppressed steady-state cortical response to 40-Hz repetitive auditory stimulation. However, systemic application of NMDA antagonists paradoxically increases this cortical response in rodents. Here, by specifically applying NMDA receptor blockade in the auditory thalamus while simultaneously measuring the acoustically driven response in 2 cortical regions, Wang and colleagues found the drop in the steady-state response that is seen in schizophrenia. These findings solve an important paradox in the field and suggest that specific thalamic neurochemical alterations may occur in the brain of individuals with schizophrenia. In addition, this work suggests that suppression of NMDA receptors in the thalamus may serve as a potential animal model for the disease.

Effect of Isoflurane on the Auditory Steady-state Response and on Consciousness in Human Volunteers 

1998 ◽  
Vol 89 (4) ◽  
pp. 844-851 ◽  
Author(s):  
Gilles Plourde ◽  
Chantal Villemure ◽  
Pierre Fiset ◽  
Vincent Bonhomme ◽  
Steven B. Backman
Keyword(s):  
Steady State ◽  
Electrical Response ◽  
Dependent Manner ◽  
Steady State Response ◽  
Concentration Dependent Manner ◽  
Isoflurane Concentration ◽  
State Response ◽  
Auditory Steady State Response ◽  
Prediction Probability ◽  
The Right

Background The auditory steady state response (ASSR) is a sustained electrical response of the brain to auditory stimuli delivered at fast rates (30-50 responses/s). The aim of this study was to evaluate the effect of 0.26-0.50% isoflurane on the ASSR and on consciousness, defined as responsiveness to verbal commands. Methods Ten volunteers (21-31 yr) participated. Isoflurane was administered at three stable, end-tidal concentrations: 0.26%, 0.38%, and 0.50%. The ASSR in response to 18,000 stimuli (500-Hz tonebursts, 10 ms, 82-dB, the right ear, 35-45 bursts/s) was recorded from the vertex with reference to the right mastoid. Recordings were made during baseline, at each isoflurane concentration, and during recovery. Results The mean (SD) ASSR amplitudes were 0.32 (0.23) microV during baseline, 0.24 (0.17) microV during 0.26% isoflurane, 0.09 (0.05) microV during 0.38% isoflurane, 0.04 (0.03) microV during 0.50% isoflurane, and 0.29 (0.33) microV during recovery. The amplitude during baseline and recovery was larger than during 0.38% and 0.50% isoflurane (P < 0.001). The amplitude at 0.26% was larger than at the other concentrations (P < 0.025). The logarithm of the ASSR amplitude was related linearly to the concentration of isoflurane (r = 0.85; P < 0.0001). The prediction probability (Pk) for loss of consciousness was 0.95 for both ASSR and measured isoflurane concentration. An ASSR amplitude < 0.07 microV was always associated with unconsciousness. Conclusions The ASSR is attenuated in a concentration-dependent manner by isoflurane. Suppression of consciousness and maximal attenuation of ASSR occur in the same isoflurane concentration range. Profound attenuation of ASSR appears to reflect unconsciousness, defined as unresponsiveness to verbal commands.

Intrathecal blockade of both NMDA and non-NMDA receptors attenuates the exercise pressor reflex in cats

1996 ◽  
Vol 80 (1) ◽  
pp. 315-322 ◽  
Author(s):  
C. M. Adreani ◽  
J. M. Hill ◽  
M. P. Kaufman
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Initial Phase ◽  
Intrathecal Injection ◽  
Secondary Phase ◽  
Receptor Blockade ◽  
Lumbosacral Spinal Cord ◽  
Ventilatory Responses ◽  
Nmda Receptor Blockade

In decerebrate unanesthetized cats we tested the hypothesis that glutamatergic-receptor blockade in the lumbosacral spinal cord attenuated the reflex increases in mean arterial pressure, inspired minute ventilation, and renal sympathetic nerve activity (RSNA) evoked by static contraction of the triceps surae muscles. Blockade of N-methyl-D-aspartate (NMDA) receptors by intrathecal injection of DL-2-amino-5-phosphonovaleric acid had no effect on the initial phase of the pressor, ventilatory, and RSNA responses to contraction but did attenuate the secondary phase of these responses. Subsequent blockade of non-NMDA receptors in the lumbosacral spinal cord by intrathecal injection of 6-cyano-7-nitroquinoxaline-2,3-dione attenuated both the initial phase of the pressor, RSNA, and ventilatory responses to contraction and the secondary phase of these responses. In addition, NMDA-receptor blockade had no effect on the pressor or RSNA responses to tendon stretch, whereas non-NMDA-receptor blockade abolished these responses. We confirmed that our results were not related to the order of the antagonists injected by performing a series of experiments in which a non-NMDA-receptor antagonist was injected first. Our findings suggest that non-NMDA receptors mediate the spinal transmission of the initial and secondary phases of the pressor, RSNA, and ventilatory responses to contraction and tendon stretch. Therefore, non-NMDA receptors in the dorsal horn appear to be involved in the spinal processing of input from mechanoreceptors and metaboreceptors. Our findings also suggest that NMDA receptors mediate the spinal transmission of the secondary phase of the pressor, RSNA, and ventilatory responses to contraction but do not mediate the spinal transmission of the responses to tendon stretch. Therefore, NMDA receptors in the dorsal horn appear to be involved in the spinal processing of input from metaboreceptors.

Competitive Inhibition of NMDA Receptor–Mediated Currents by Extracellular Calcium Chelators

2000 ◽  
Vol 84 (2) ◽  
pp. 693-697 ◽  
Author(s):  
Nansheng Chen ◽  
Timothy H. Murphy ◽  
Lynn A. Raymond
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Dose Response ◽  
Response Curve ◽  
Competitive Inhibition ◽  
Response Shift ◽  
Dose Response Curve ◽  
Hek 293 ◽  
Electrophysiological Recordings ◽  
The Right

Calcium chelators have been widely used in electrophysiological recordings of N-methyl-d-aspartate (NMDA) receptor–mediated currents, as well as in studies of excitotoxicity. Intracellularly applied calcium chelators are known to inhibit, at least in part, such calcium-dependent processes as calmodulin-dependent inactivation, calcineurin-dependent desensitization, and rundown of NMDA receptors. On the other hand, the functional consequences and potential nonspecific effects of extracellularly applied chelators have not been extensively investigated. In whole-cell patch-clamp recordings from human embryonic kidney (HEK) 293 cells transiently transfected with recombinant NMDA receptors, we found that addition of calcium chelators such as EGTA shifted the glutamate dose-response curve to the right, from an EC50 for NR1A/NR2A of 8 μM in 1.8 mM Ca2+ to ∼24 μM in a solution containing nominal 0 Ca2+/5 mM EGTA and further to ∼80 μM in 20 mM EGTA. A similar shift in glutamate dose-response was observed for NR1A/NR2B currents. This dose-response shift was not due to a decrease in extracellular Ca2+ concentration because there was no change in the glutamate EC50 at Ca2+concentrations ranging from 10 mM to nominal 0/200 μM EGTA. Moreover, addition of 5 mM EGTA fully chelated with 6.8 mM Ca2+ did not produce any shift in the glutamate dose-response curve. We propose that calcium chelators, containing four free carboxyl moieties, competitively inhibit glutamate binding to NMDA receptors.

Activation of NMDA receptors linked to modulation of voltage-gated ion channels and functional implications

2003 ◽  
Vol 284 (3) ◽  
pp. C757-C768 ◽  
Author(s):  
S. F. Davis ◽  
C. L. Linn
Keyword(s):  
Steady State ◽  
Membrane Potential ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Receptor Activation ◽  
Calcium Currents ◽  
Horizontal Cells ◽  
Voltage Gated ◽  
Functional Implications ◽  
Nmda Receptor Activation

Catfish ( Ictalurus punctatus) cone horizontal cells contain N-methyl-d-aspartate (NMDA) receptors, the function of which has yet to be determined. In the present study, we have examined the effect of NMDA receptor activation on voltage-gated ion channel activity. NMDA receptor activation produced a long-term downregulation of voltage-gated sodium and calcium currents but had no effect on the delayed rectifying potassium current. NMDA's effect was eliminated in the presence of AP-7. To determine whether NMDA receptor activation had functional implications, isolated catfish cone horizontal cells were current clamped to mimic the cell's physiological response. When horizontal cells were depolarized, they elicited a single depolarizing overshoot and maintained a depolarized steady state membrane potential. NMDA reduced the amplitude of the depolarizing overshoot and increased the depolarized steady-state membrane potential. Both effects of NMDA were eliminated in the presence of AP-7. These results support the hypothesis that activation of NMDA receptors in catfish horizontal cells may affect the type of visual information conveyed through the distal retina.

scholarly journals Neurophysiological Evaluation of Right-Ear Advantage During Dichotic Listening

2021 ◽  
Vol 12 ◽  
Author(s):  
Keita Tanaka ◽  
Bernhard Ross ◽  
Shinya Kuriki ◽  
Tsuneo Harashima ◽  
Chie Obuchi ◽  
...  
Keyword(s):  
Steady State ◽  
Auditory Cortex ◽  
Dichotic Listening ◽  
Steady State Response ◽  
State Response ◽  
Auditory Steady State Response ◽  
Left And Right ◽  
Ear Advantage ◽  
Right Ear Advantage ◽  
The Right

Right-ear advantage refers to the observation that when two different speech stimuli are simultaneously presented to both ears, listeners report stimuli more correctly from the right ear than the left. It is assumed to result from prominent projection along the auditory pathways to the contralateral hemisphere and the dominance of the left auditory cortex for the perception of speech elements. Our study aimed to investigate the role of attention in the right-ear advantage. We recorded magnetoencephalography data while participants listened to pairs of Japanese two-syllable words (namely, “/ta/ /ko/” or “/i/ /ka/”). The amplitudes of the stimuli were modulated at 35 Hz in one ear and 45 Hz in the other. Such frequency-tagging allowed the selective quantification of left and right auditory cortex responses to left and right ear stimuli. Behavioral tests confirmed the right-ear advantage, with higher accuracy for stimuli presented to the right ear than to the left. The amplitude of the auditory steady-state response was larger when attending to the stimuli compared to passive listening. We detected a correlation between the attention-related increase in the amplitude of the auditory steady-state response and the laterality index of behavioral accuracy. The right-ear advantage in the free-response dichotic listening was also found in neural activities in the left auditory cortex, suggesting that it was related to the allocation of attention to both ears.

scholarly journals Algunos errores numéricos en la respuesta del estado estable de sistemas mecánicos vibratorios

2019 ◽  
pp. 1-9
Author(s):  
Benjamín Vázquez-González ◽  
Homero Jiménez-Rabiela ◽  
José Luis Ramírez-Cruz ◽  
Adrian Gustavo Bravo-Acosta
Keyword(s):  
Steady State ◽  
Mechanical Vibration ◽  
Numerical Algorithms ◽  
Steady State Response ◽  
High Excitation ◽  
State Response ◽  
Oscillating Systems ◽  
The Common ◽  
Excitation Frequencies ◽  
The Right

In this work numerical simulation results are shown for the steady state response of linear mechanical oscillating systems and the numerical errors that can be present when some numerical algorithms are used to perform the simulations. For some numerical parameters, the mechanical oscillating system with or without damping response, does not converge to the expected steady state response; this discrepancy is not easily detected when the performance of the system is on the range of high excitation frequencies, due that for of high excitation frequencies the amplitude in the steady state response reaches very small values. We perform the time response of the system using conventionally numerical methods included in the common programming platforms, and the result is that using the same algorithm in different platforms the error is the same; selecting other numeric algorithm the result in satisfactory. Non linear forced mechanical vibration systems; behave like linear systems for some frequency range, then is very useful to obtain the right or correct responses in the steady state response for the linear system, this is fundamental for forward studies, the right analysis is based on the selected numeric algorithm.

NMDA Receptor Blockade in the Superior Colliculus Increases Receptive Field Size Without Altering Velocity and Size Tuning

2003 ◽  
Vol 90 (1) ◽  
pp. 110-119 ◽  
Author(s):  
Khaleel A. Razak ◽  
Lihua Huang ◽  
Sarah L. Pallas
Keyword(s):  
Nmda Receptor ◽  
Receptive Field ◽  
Superior Colliculus ◽  
Nmda Receptors ◽  
Field Size ◽  
Stimulus Velocity ◽  
Evolutionary Changes ◽  
Nmda Receptor Blockade ◽  
Nmda Receptor Function ◽  
Injured Region

Neonatal brain injury triggers compensatory processes that can be adaptive or detrimental, but little is known about the mechanisms of compensation or how they might affect the response properties of neurons within the injured region. We have studied this issue in a rodent model. Partial ablation of the hamster superior colliculus (SC) at birth results in a compressed but complete visual field map in the remaining SC and a compensatory conservation of receptive field (RF) size and stimulus velocity and size tuning. The circuit underlying stimulus tuning in this system or its preservation after brain lesions is not known. Our previous work has shown that N-methyl-d-aspartate (NMDA) receptors are necessary for the development and conservation of RF size after partial SC ablation. In this study, we examined whether NMDA receptor function is also necessary for the development and conservation of stimulus velocity and size tuning. We found that velocity and size tuning were unaffected by chronic postnatal blockade of NMDA receptors and the resulting increases in RF size. Thus NMDA receptors in the SC are not necessary for the development of stimulus velocity and size tuning or in the compensatory maintenance of these properties following brain damage. These results suggest that stimulus velocity and size tuning may arise in the retina or from NMDA receptor-independent circuitry intrinsic to SC. The lack of conflict between NMDA receptor activity-dependent and -independent processes may allow conservation of some RF properties while others change during injury-induced or evolutionary changes in afferent/target convergence.

Recruitment of GABAA inhibition in rat neocortex is limited and not NMDA dependent

1995 ◽  
Vol 74 (6) ◽  
pp. 2329-2335 ◽  
Author(s):  
D. S. Ling ◽  
L. S. Benardo
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Pyramidal Neurons ◽  
Reversal Potential ◽  
Cell Voltage ◽  
Receptor Blockade ◽  
Gamma Aminobutyric Acid ◽  
Postsynaptic Currents ◽  
Nmda Receptor Blockade ◽  
Layer V

1. The recruitment of evoked fast inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs) was examined using whole cell voltage-clamp recordings from layer V pyramidal neurons in slices of rat somatosensory cortex. Synaptic currents were evoked with graded electrical stimulation to assess the relative activation of IPSCs and EPSCs. Fast GABAA ergic IPSCs were selectively recorded by holding cells at potentials equal to EPSC reversal (approximately 0 mV). EPSCs were likewise isolated by holding cells at IPSC reversal potential (about -75 mV). 2. As stimulus intensities were increased, the magnitude of the postsynaptic currents also increased. Over the range of stimuli applied (2-10 V), EPSCs did not exhibit an upper limit. However, fast gamma-aminobutyric acid-A (GABAA-mediated IPSCs reached a maximum at intensities approximately 2 times threshold. 3. The limit on fast inhibition was unresponsive to alterations in N-methyl-D-aspartate (NMDA)-mediated excitation. Exposure to nominally magnesium-free solutions or to the NMDA antagonist 3-[(RS)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid did not affect the fast IPSC maximum. Shifts in the input-output curves for submaximal activation of IPSCs were seen, which were attributed to polysynaptic excitation. 4.Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (non-NMDA) receptors with 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) completely abolished synaptically driven, fast GABAA-mediated inhibition. These findings suggested that neocortical inhibitory cells could be driven exclusively through non-NMDA transmission. 5. By comparison, in hippocampal CA1 pyramidal neurons maximal fast inhibition was sensitive to both NMDA and non-NMDA receptor blockade. 6. The results in neocortex were corroborated by direct intracellular recordings from layer V-VI interneurons. Non-NMDA receptor blockade with CNQX prevented synaptic activation of action potentials in these cells, even during cotreatment with magnesium-free solution. 7. Together, these results suggest that recruitment of GABA(A) ergic IPSCs in neocortex is ultimately driven via glutamatergic afferents arriving at non-NMDA receptors on interneurons. Properties limiting fast inhibition would favor the propagation of enhanced excitatory activity through the neuronal network.

Pressure-volume response of isolated living main pulmonary artery in dogs

1965 ◽  
Vol 20 (4) ◽  
pp. 675-682 ◽  
Author(s):  
Wallace G. Frasher ◽  
Sidney S. Sobin
Keyword(s):  
Steady State ◽  
Stress Relaxation ◽  
Pulmonary Artery ◽  
Main Pulmonary Artery ◽  
Single Mode ◽  
Elastic Response ◽  
State Response ◽  
Response Coefficient ◽  
Volume Response ◽  
The Right

Isolation of the main pulmonary artery by obturation of the right and left branches under conditions which maintained vasal circulation to the wall was achieved by extracorporeal circulation. Pressure-volume response of the segment was measured directly using a reciprocating essentially sinusoidal volume input at rates of 90, 45, and 180 cycles/min. Using volumes which generated physiologic pressures, a steady-state response starting from rest occurred in 300—500 cycles. At steady state the pressure-volume response was linear and unchanged by these cycling rates. The relaxation pattern during the initial phase was consistent with a single mode of response and closely duplicated the stress-relaxation pattern of a single noncycled input of the same volume. In 34 experiments in 11 animals steady-state volume distensibility (DeltaV x 100/V0 DeltaP) was 2.51% cm H2O. Segment geometry was preserved by luminal casting. An ellipsoidal configuration was apparent in the distended state. pulmonary-artery distensibility; mechanical behavior of arteries; stress-relaxation; geometry of arteries; tethering; viscoelastic properties of arteries; dynamic elastic response; coefficient of distensibility Submitted on June 16, 1964

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