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

2001 ◽  
Vol 86 (2) ◽  
pp. 871-880 ◽  
Author(s):  
Huiming Zhang ◽  
Jack B. Kelly

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.

1995 ◽  
Vol 12 (5) ◽  
pp. 819-825 ◽  
Author(s):  
Hong-Feng Gao ◽  
Gang-Yi Wu ◽  
Barrie J. Frost ◽  
Shu-Rong Wang

AbstractRotundal neurons in pigeons (Columba livia) were examined for the effects of glutamate and its agonists NMDA and AMPA, antagonists CPP and CNQX, as well as of GABA and its antagonist bicuculline, on visual and tectal stimulation-evoked responses. Glutamate applied by iontophoresis excited all 48 rotundal cells tested, and this excitation was blocked by CNQX but not by CPP in 98% of cases, with 2% of cells being blocked by either CNQX or CPP. Out of 21 cells excited by AMPA, 20 were also excited by NMDA, indicating that AMPA and NMDA receptors may coexist in most rotundal cells. Action potentials were evoked in 36 additional cells by electrical stimulation applied to the tectum and they were also blocked by CNQX but not CPP. Visual responses recorded from a further eight luminance units and 21 motion-sensitive units were also blocked by CNQX and not CPP. On the other hand, GABA inhibited visual responses as well as responses evoked by tectal stimulation. An inhibitory period following tectal stimulation was eliminated by bicuculline. Taken together, these results indicate that glutamate may be an excitatory transmitter acting predominantly through non-NMDA receptors (AMPA receptors) in tectorotundal transmission. Meanwhile, GABA may be an inhibitory transmitter in the pigeon nucleus rotundus.


2018 ◽  
Vol 1 (3) ◽  
pp. e00021
Author(s):  
V.V. Grigoriev ◽  
E.V. Bovina

The obtained results show that endogenous peptides play an important role in the regulation of the glutamatergic mediator system of the brain. They act in extremely low concentrations, starting at 1 × 10–14 M, their effects are concentration-dependent and reversible, thus indicating the exclusive specificity of the corresponding receptors. The range of their influence on responses of postsynaptic glutamate receptors is rather narrow and, as a rule, does not exceed 60-70% of control. We have demonstrated for the first time that CLIP blocks NMDA receptors and potentiates AMPA receptors in a wide range of concentrations (6 orders of magnitude); this is very important for manifestation of memory-stimulating effect. Somatostatin blocking NMDA receptors and potentiating AMPA receptors, also plays an important role in the mechanisms of memory formation. Obviously, there is a great similarity in the action of both peptides on AMPA and NMDA receptors. Thus our results provide the first information about regulation of including cognitive processes and memory mechanisms by endogenous compounds. This mechanism particularly involves regulation of AMPA and NMDA receptors in the brain.


2007 ◽  
Vol 07 (02) ◽  
pp. 229-246
Author(s):  
ROUSTEM MIFTAHOF ◽  
N. R. AKHMADEEV

The role of cotransmission by α-amino-3-hydroxy-5-methyl-4-isoxalose propionic acid (AMPA), L-aspartate, N-methyl-D-aspartate (NMDA), and acetylcholine (ACh) as well as the coexpression of AMPA, NMDA, and nicotinic ACh (nACh) receptors on the electrophysiological activity of the primary sensory (AH) and motor (S) neurons of the enteric nervous system are numerically assessed. Results of computer simulations showed that AMPA and L-Asp alone can induce fast action potentials of short duration on AH and S neurons. Costimulation of nACh and AMPA receptors on the soma of the S neuron resulted in periodic spiking activity. A characteristic biphasic response was recorded from the AH neuron after coactivation of AMPA and NMDA receptors. Glutamate alone acting on NMDA receptors caused prolonged depolarization of the AH neuron and failed to depolarize the S neuron. Cojoint stimulation of the AMPA or nACh receptors was required to produce the effect of glutamate. The overall electrical response of neurons to the activation of NMDA receptors was long-term depolarization. Acetylcholine, AMPA, and glutamate acting alone or cojointly enhanced phasic contraction of the longitudinal smooth muscle. Treatment of neurons with AMPA, NMDA, and nACh receptor antagonists revealed intricate properties of the AH and S neurons. Application of MK-801, D-AP5, and CPP reduced the excitability of the AH neuron and totally abolished electrical activity in the S neuron. The information gained into the cotransmission by excitatory amino acids and acetylcholine in the enteric nervous system may be beneficial in the development of novel effective therapeutics to treat diseases associated with altered visceral nociception, i.e. irritable bowel syndrome.


1998 ◽  
Vol 80 (4) ◽  
pp. 1686-1701 ◽  
Author(s):  
R. Michael Burger ◽  
George D. Pollak

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.


2007 ◽  
Vol 97 (2) ◽  
pp. 1368-1378 ◽  
Author(s):  
S. V. Voytenko ◽  
A. V. Galazyuk

The central nucleus of the inferior colliculus (IC) is a major integrative center in the central auditory system. It receives information from both the ascending and descending auditory pathways. To determine how single IC neurons integrate information over a wide range of sound frequencies and sound levels, we examined their intracellular responses to frequency-modulated (FM) sounds in awake little brown bats ( Myotis lucifugus). Postsynaptic potentials were recorded in response to downward FM sweeps of the range typical for little brown bats (80–20 kHz) and to three FM subcomponents (80–60, 60–40, and 40–20 kHz). The majority of recorded neurons responded to the 80- to 20-kHz downward FM sweep with a complex response. In this response an initial hyperpolarization was followed by depolarization with or without spike followed by hyperpolarization. Intracellular recordings in response to three FM subcomponents revealed that these neurons receive excitatory and inhibitory inputs from a wide range of sound frequencies. One third of IC neurons performed nearly linear temporal summation across a wide range of sound frequencies, whereas two thirds of IC neurons exhibited nonlinear summation with different degrees of nonlinearity. Some IC neurons showed different latencies of postsynaptic potentials in response to different FM subcomponents. Often responses to the later FM subcomponent occurred before responses to the earlier ones. This phenomenon may be responsible for response selectivity of IC neurons to FM sweeps.


1998 ◽  
Vol 79 (6) ◽  
pp. 2986-2998 ◽  
Author(s):  
Evanna L. Gleason ◽  
Nicholas C. Spitzer

Gleason, Evanna L. and Nicholas C. Spitzer. AMPA and NMDA receptors expressed by differentiating Xenopus spinal neurons. J. Neurophysiol. 79: 2986–2998, 1998. N-methyl-d-aspartate (NMDA) receptors are often the first ionotropic glutamate receptors expressed at early stages of development and appear to influence neuronal differentiation by mediating Ca2+ influx. Although less well studied, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors also can generate Ca2+ elevations and may have developmental roles. We document the presence of AMPA and NMDA class receptors and the absence of kainate class receptors with whole cell voltage-clamp recordings from Xenopus embryonic spinal neurons differentiated in vitro. Reversal potential measurements indicate that AMPA receptors are permeable to Ca2+ both in differentiated neurons and at the time they first are expressed. The P Ca/ P monocation of 1.9 is close to that of cloned Ca2+-permeable AMPA receptors expressed in heterologous systems. Ca2+ imaging reveals that Ca2+ elevations are elicited by AMPA or NMDA in the absence of Mg2+. The amplitudes and durations of these agonist-induced Ca2+ elevations are similar to those of spontaneous Ca2+ transients known to act as differentiation signals in these cells. Two sources of Ca2+ amplify AMPA- and NMDA-induced Ca2+ elevations. Activation of voltage-gated Ca2+ channels by AMPA- or NMDA-mediated depolarization contributes ∼15 or 30% of cytosolic Ca2+ elevations, respectively. Activation of either class of receptor produces elevations of Ca2+ that elicit further release of Ca2+ from thapsigargin-sensitive but ryanodine-insensitive stores, contributing an additional ∼30% of Ca2+ elevations. Voltage-clamp recordings and Ca2+ imaging both show that these spinal neurons express functional AMPA receptors soon after neurite initiation and before expression of NMDA receptors. The Ca2+ permeability of AMPA receptors, their ability to generate significant elevations of [Ca2+]i, and their appearance before synapse formation position them to play roles in neural development. Spontaneous release of agonists from growth cones is detected with glutamate receptors in outside-out patches, suggesting that spinal neurons are early, nonsynaptic sources of glutamate that can influence neuronal differentiation in vivo.


2002 ◽  
Vol 88 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Sabrina Wang ◽  
Zhengping Jia ◽  
John Roder ◽  
Timothy H. Murphy

AMPA-type glutamate receptors are normally Ca2+ impermeable due to the expression of the GluR2 receptor subunit. By using GluR2 null mice we were able to detect miniature synaptic Ca2+ transients (MSCTs) associated with AMPA-type receptor-mediated miniature synaptic currents at single synapses in primary cortical cultures. MSCTs and associated Ca2+ transients were monitored under conditions that isolated responses mediated by AMPA or N-methyl-d-aspartate (NMDA) receptors. As expected, addition of the antagonist 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX, 3 μM) blocked the AMPA receptor-mediated MSCTs. Voltage-gated Ca2+channels did not contribute to AMPA MSCTs because CdCl2 (0.1–0.2 mM) did not significantly alter the frequency or the amplitude of the MSCTs. The amplitude of AMPA MSCTs appeared to be regulated independently from event frequency since the two measures were not correlated ( R = 0.023). Synapses were identified that only expressed MSCTs attributed to either NMDA or AMPA receptors. At synapses with only NMDA responses, MSCT amplitude was significantly lower (by 40%) than synapses expressing both NMDA and AMPA responses. At synapses that showed MSCTs mediated by both AMPA and NMDA receptors, the amplitude of the transients in each condition was positively correlated ( R = 0.94). Our results suggest that when AMPA and NMDA receptors are co-expressed at synapses, mechanisms exist to ensure proportional scaling of each receptor type that are distinct from the presynaptic factors controlling the frequency of miniature release.


2004 ◽  
Vol 91 (5) ◽  
pp. 2194-2204 ◽  
Author(s):  
Huiming Zhang ◽  
Shu Hui Wu ◽  
Jack B. Kelly

The role of potassium channels in regulating spontaneous firing and sound-evoked responses in the central nucleus of the inferior colliculus was studied by recording single-unit activity before and during iontophoretic application of a nonspecific potassium channel blocker, tetraethylammonium (TEA). Tone bursts and sinusoidal amplitude-modulated tones were used to evoke auditory responses. Our results show that release of TEA increased the width of spikes for all neurons tested. There was an increase in spontaneous firing for most of the neurons. There was also an increase in responses to tone bursts for most of the neurons, although in some cases there was a reduction in the evoked responses. TEA also increased the firing rate in responses to sinusoidal amplitude-modulated sounds in the majority of the neurons tested. For some neurons, the change in firing reduced the selectivity of responses for particular rates of modulation. There was also a reduction in the synchrony of action potentials to the modulation envelope in many cells. Our results show that potassium channels are important for regulating the strength of sound-evoked responses and the level of spontaneous activity, and determining the temporal properties of responses to amplitude-modulated sounds.


Sign in / Sign up

Export Citation Format

Share Document