Analysis of the Role of Inhibition in Shaping Responses to Sinusoidally Amplitude-Modulated Signals in the Inferior Colliculus

Burger, R. Michael and George D. Pollak. Analysis of the role of inhibition in shaping responses to sinusoidally amplitude-modulated signals in the inferior colliculus. J. Neurophysiol. 80: 1686–1701, 1998. Neurons in the central nucleus of the inferior colliculus (ICc) typically respond with phase-locked discharges to low rates of sinusoidal amplitude-modulated (SAM) signals and fail to phase-lock to higher SAM rates. Previous studies have shown that comparable phase-locking to SAM occurs in the dorsal nucleus of the lateral lemniscus (DNLL) and medial superior olive (MSO) of the mustache bat. The studies of MSO and DNLL also showed that the restricted phase-locking to low SAM rates is created by the coincidence of phase-locked excitatory and inhibitory inputs that have slightly different latencies. Here we tested the hypothesis that responses to SAM in the mustache bat IC are shaped by the same mechanism that shapes responses to SAM in the two lower nuclei. We recorded responses from ICc neurons evoked by SAM signals before and during the iontophoretic application of several pharmacological agents: bicuculline, a competitive antagonist for γ-aminobutyric acid-A (GABAA) receptors; strychnine, a competitive antagonist for glycine receptors; the GABAB receptor blocker, phaclofen, and the N-methyl-d-aspartate (NMDA) receptor blocker, (−)-2-amino-5-phosphonopentanoic acid (AP5). The hypothesis that inhibition shapes responses to SAM signals in the ICc was not confirmed. In >90% of the ICc neurons tested, the range of SAM rates to which they phase-locked was unchanged after blocking inhibition with bicuculline, strychnine or phaclofen, applied either individually or in combination. We also considered the possibility that faster α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors follow high temporal rates of incoming excitation but that the slower NMDA receptors could follow only lower rates. Thus at higher SAM rates, NMDA receptors might generate a sustained excitation that “smears” the phase-locked excitation generated by the AMPA receptors. The NMDA hypothesis, like the inhibition hypothesis, was also not confirmed. In none of the cells that we tested did the application of AP5 by itself, or in combination with bicuculline, cause an increase in the range of SAM rates that evoked phase-locking. These results illustrate that the same response property, phase-locking restricted to low SAM rates, is formed in more than one way in the auditory brain stem. In the MSO and DNLL, the mechanism is coincidence of phase-locked excitation and inhibition, whereas in ICc the same response feature is formed by a different but unknown mechanism.

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Potentiation of Synaptic AMPA Receptors Induced by the Deletion of NMDA Receptors Requires the GluA2 Subunit

Journal of Neurophysiology ◽

10.1152/jn.00725.2010 ◽

2011 ◽

Vol 105 (2) ◽

pp. 923-928 ◽

Cited By ~ 14

Author(s):

Wei Lu ◽

John A. Gray ◽

Adam J. Granger ◽

Matthew J. During ◽

Roger A. Nicoll

Keyword(s):

Nmda Receptors ◽

Single Cell ◽

Ampa Receptors ◽

Substantial Evidence ◽

Ampar Trafficking

Deletion of N-methyl-d-aspartate receptors (NMDARs) early in development results in an increase in the number of synaptic AMPA receptors (AMPARs), suggesting a role for NMDARs in negatively regulating AMPAR trafficking at developing synapses. Substantial evidence has shown that AMPAR subunits function differentially in AMPAR trafficking. However, the role of AMPAR subunits in the enhancement of AMPARs following NMDAR ablation remains unknown. We have now performed single-cell genetic deletions in double-floxed mice in which the deletion of GluN1 is combined with the deletion of GluA1 or GluA2. We find that the AMPAR enhancement following NMDAR deletion requires the GluA2 subunit, but not the GluA1 subunit, indicating a key role for GluA2 in the regulation of AMPAR trafficking in developing synapses.

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Role of AMPA Receptor Desensitization and the Side Effects of a DMSO Vehicle on Reticulospinal EPSPs and Locomotor Activity

Journal of Neurophysiology ◽

10.1152/jn.00201.2005 ◽

2005 ◽

Vol 94 (6) ◽

pp. 3951-3960 ◽

Cited By ~ 27

Author(s):

Nataliya A. Tsvyetlynska ◽

Russell H. Hill ◽

Sten Grillner

Keyword(s):

Nmda Receptors ◽

Ampa Receptor ◽

Ampa Receptors ◽

Pattern Generation ◽

Network Activity ◽

Excitatory Postsynaptic Potential ◽

Receptor Desensitization ◽

Neuronal Network Activity ◽

The Brain

Activation of the vertebrate locomotor network is mediated by glutamatergic synaptic drive, normally initiated by the brain stem. Previous investigations have studied the role of glutamate receptors, especially NMDA receptors, in generating and regulating locomotor pattern generation. Few studies, however, have focused on the role of AMPA receptors in shaping network activity, especially with regard to their rapid desensitization. It is important to determine whether AMPA receptor desensitization plays a role in regulating neuronal network activity. We examined this question on both the network and synaptic levels in the lamprey ( Lampetra fluviatilis) spinal cord using a selective and potent inhibitor of AMPA receptor desensitization, cyclothiazide (CTZ). The solvent dimethyl sulfoxide (DMSO) is commonly used to dissolve this drug, as well as many others. Unexpectedly, the vehicle alone already at 0.02%, but not at 0.01%, caused significant increases in excitatory postsynaptic potential (EPSP) amplitudes and NMDA-induced locomotor frequency. The results indicate that DMSO may have a profound influence when used ≥0.02%, a concentration 10–50 times less than that most commonly used. Subsequently we applied CTZ concentrations ≤10 μM (DMSO ≤0.01%). CTZ (1.25–5 μM) caused an appreciable and significant increase in EPSPs mediated by non-NMDA receptors and in both AMPA- and NMDA-induced locomotor frequency, but no effects on EPSPs mediated by NMDA receptors. From the effects of CTZ it is apparent that AMPA receptor desensitization plays an important role in determining locomotor frequency and that this is likely a result of its limiting function on AMPA receptor–mediated EPSPs.

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Glutamatergic receptors at developing synapses: The role of GluN3A-containing NMDA receptors and GluA2-lacking AMPA receptors

European Journal of Pharmacology ◽

10.1016/j.ejphar.2013.04.056 ◽

2013 ◽

Vol 719 (1-3) ◽

pp. 107-111 ◽

Cited By ~ 20

Author(s):

Tifei Yuan ◽

Camilla Bellone

Keyword(s):

Nmda Receptors ◽

Ampa Receptors

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AMPA and NMDA Receptors Regulate Responses of Neurons in the Rat's Inferior Colliculus

Journal of Neurophysiology ◽

10.1152/jn.2001.86.2.871 ◽

2001 ◽

Vol 86 (2) ◽

pp. 871-880 ◽

Cited By ~ 42

Author(s):

Huiming Zhang ◽

Jack B. Kelly

Keyword(s):

Nmda Receptors ◽

Inferior Colliculus ◽

Ampa Receptors ◽

Action Potentials ◽

Drug Application ◽

Pronounced Effect ◽

Central Nucleus ◽

Wide Range ◽

Ampa And Nmda Receptors ◽

Excitatory Responses

The contribution of N-methyl-d-aspartate (NMDA) and AMPA receptors to auditory responses in the rat's inferior colliculus was examined by recording single-unit activity before, during, and after local iontophoretic application of receptor-specific antagonists. Tone bursts and sinusoidal amplitude modulated sounds were presented to one ear, and recordings were made from the contralateral central nucleus of inferior colliculus (ICC). The receptor specific antagonists, (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) for NMDA receptors and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX) for AMPA receptors, were released at the recording site through a multi-barreled pipette. For most neurons, either CPP or NBQX alone resulted in a reversible reduction in the number of action potentials evoked by tonal stimulation. For neurons with an onset response pattern, NBQX either completely eliminated or greatly reduced the number of action potentials. CPP also reduced the number of action potentials but had a less pronounced effect than NBQX. For neurons with a sustained firing pattern, NBQX reduced the total number of action potentials, but had a preferential effect on the early part (first 10–20 ms) of the response. CPP also resulted in a reduction in the total number of action potentials, but had a more pronounced effect on the later part (>20 ms) of the response. These results indicate that both AMPA and NMDA receptors contribute to sound evoked excitatory responses in the ICC. They have a selective influence on early and late components of tone-evoked responses. Both receptor types are involved in generating excitatory responses across a wide range of sound pressure levels as indicated by rate level functions obtained before and during drug application. In addition, both CPP and NBQX reduced responses to sinusoidal amplitude modulated sounds. The synchrony of firing to the modulation envelope as measured by vector strength at different rates of modulation was not greatly affected by either CPP or NBQX in spite of the decrease in firing rate.

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Possible Role of N-Methyl-D-Aspartate Receptors in Physiology and Pathophysiology of Cardiovascular System

Serbian Journal of Experimental and Clinical Research ◽

10.1515/sjecr-2017-0010 ◽

2019 ◽

Vol 20 (1) ◽

pp. 3-13 ◽

Cited By ~ 1

Author(s):

Ivan Srejovic ◽

Vladimir Jakovljevic ◽

Vladimir Zivkovic ◽

Dragan Djuric

Keyword(s):

Nmda Receptors ◽

Cardiovascular System ◽

Ampa Receptors ◽

Heart Function ◽

Cell Types ◽

Receptor Activation ◽

Simultaneous Action ◽

Cardiovascular Disorders ◽

Voltage Dependent

Abstract N-methyl-D-aspartate (NMDA) receptors belong to ionotropic glutamate receptor family, together with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, kainite receptors and δ-receptors. All of these receptors are tetramers composed of four subunits. NMDA receptors have several unique features in relation to other ionotropic glutamate receptors: requirement for simultaneous action of two coagonists, glutamate and glycine; dual control of receptor activation, ligand-dependent (by glutamate and glycine) and voltage-dependent (Mg2+ block) control; and influx of considerable amounts of Ca2+ following receptor activation. Increasing number of researches deals with physiological and pathophysiological roles of NMDA receptors outside of nerve tissues, especially in the cardiovascular system. NMDA receptors are found in all cell types represented in cardiovascular system, and their overstimulation in pathological conditions, such as hyperhomocysteinemia, is related to a range of cardiovascular disorders. On the other hand we demonstrated that blockade of NMDA receptors depresses heart function. There is a need for the intensive study of NMDA receptor in cardiovascular system as potential theraputical target both in prevention and treatment of cardiovascular disorders.

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The Role of Quercetin in Gene Expression of GluR1 Subunit of AMPA Receptors, and NR2A and NR2B Subunits of NMDA Receptors in Kainic Acid Model of Seizure in Mice

Iranian Red Crescent Medical Journal ◽

10.5812/ircmj.42415 ◽

2016 ◽

Vol 19 (5) ◽

Cited By ~ 2

Author(s):

Sahar Moghbelinejad ◽

Ghazaleh Mohammadi ◽

Fatemeh Khodabandehloo ◽

Reza Najafipour ◽

Taghi Naserpour ◽

...

Keyword(s):

Gene Expression ◽

Nmda Receptors ◽

Kainic Acid ◽

Ampa Receptors ◽

Glur1 Subunit

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Novel Approach to the Role of NMDA Receptors in Traumatic Brain Injury

CNS & Neurological Disorders - Drug Targets ◽

10.2174/18715273113126660196 ◽

2014 ◽

Vol 13 (4) ◽

pp. 567-573 ◽

Cited By ~ 40

Author(s):

Esther Shohami ◽

Anat Biegon

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Nmda Receptors ◽

Novel Approach

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The role of adenosine in the regulation of cerebral blood flow: antagonistic effects of theophylline, an adenosine receptor blocker, on adenosine- and hypoxia-induced vasodilation of rat cerebral microvessels

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)58912-0 ◽

1986 ◽

Vol 40 ◽

pp. 31

Author(s):

Seiji Morii ◽

Al C. Ngai ◽

H. Richard Winn

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Adenosine Receptor ◽

Receptor Blocker ◽

Cerebral Microvessels ◽

Antagonistic Effects

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Phase-Locked Responses to Pure Tones in the Inferior Colliculus

Journal of Neurophysiology ◽

10.1152/jn.00497.2005 ◽

2006 ◽

Vol 95 (3) ◽

pp. 1926-1935 ◽

Cited By ~ 70

Author(s):

Liang-Fa Liu ◽

Alan R. Palmer ◽

Mark N. Wallace

Keyword(s):

Guinea Pig ◽

Inferior Colliculus ◽

Phase Locking ◽

Single Units ◽

Central Nucleus ◽

Dorsal Cortex ◽

Upper Limits ◽

Ascending Pathways ◽

Pure Tones ◽

The Brain

In the auditory system, some ascending pathways preserve the precise timing information present in a temporal code of frequency. This can be measured by studying responses that are phase-locked to the stimulus waveform. At each stage along a pathway, there is a reduction in the upper frequency limit of the phase-locking and an increase in the steady-state latency. In the guinea pig, phase-locked responses to pure tones have been described at various levels from auditory nerve to neocortex but not in the inferior colliculus (IC). Therefore we made recordings from 161 single units in guinea pig IC. Of these single units, 68% (110/161) showed phase-locked responses. Cells that phase-locked were mainly located in the central nucleus but also occurred in the dorsal cortex and external nucleus. The upper limiting frequency of phase-locking varied greatly between units (80−1,034 Hz) and between anatomical divisions. The upper limits in the three divisions were central nucleus, >1,000 Hz; dorsal cortex, 700 Hz; external nucleus, 320 Hz. The mean latencies also varied and were central nucleus, 8.2 ± 2.8 (SD) ms; dorsal cortex, 17.2 ms; external nucleus, 13.3 ms. We conclude that many cells in the central nucleus receive direct inputs from the brain stem, whereas cells in the external and dorsal divisions receive input from other structures that may include the forebrain.

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