The physiology of excitatory amino acids in the vertebrate central nervous system

Mayer, Mark L.; Westbrook, Gary L.

doi:10.1016/0301-0082(87)90011-6

Cited by 1,656 publications

(685 citation statements)

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“…Indeed, backpropagating spikes might lead to Ca 2+ entry through the activation of voltage-gated Ca 2+ channels and/or by temporarily removing the Mg 2+ block of N-methyl--aspartate (NMDA) channels. 43 Considering the impact of intracellular Ca 2+ levels on various forms of synaptic plasticity, 3 it is important to determine how inhibitory synaptic inputs affect the dendritic participation in somatic APs under in vivo conditions where the cortical circuitry is intact. To this end, we performed intracellular recordings of morphologically-identified neocortical pyramidal neurons in anaesthetized cats and compared APs evoked by synaptic inputs, antidromic invasion, or direct current injection.…”

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confidence: 99%

Inhibitory control of somatodendritic interactions underlying action potentials in neocortical pyramidal neurons in vivo: An intracellular and computational study

Paré¹,

Lang²,

Destexhe³

1998

Neuroscience

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Abstract--The effect of synaptic inputs on somatodendritic interactions during action potentials was investigated, in the cat, using in vivo intracellular recording and computational models of neocortical pyramidal cells. An array of 10 microelectrodes, each ending at a different cortical depth, was used to preferentially evoke synaptic inputs to different somatodendritic regions. Relative to action potentials evoked by current injection, spikes elicited by cortical microstimuli were reduced in amplitude and duration, with stimuli delivered at proximal (somatic) and distal (dendritic) levels evoking the largest and smallest decrements, respectively. When the inhibitory postsynaptic potential reversal was shifted to around 50 mV by recording with KCl pipettes, synaptically-evoked spikes were significantly less reduced than with potassium acetate or cesium acetate pipettes, suggesting that spike decrements are not only due to a shunt, but also to voltage-dependent effects. Computational models of neocortical pyramidal cells were built based on available data on the distribution of active currents and synaptic inputs in the soma and dendrites. The distribution of synapses activated by extracellular stimulation was estimated by matching the model to experimental recordings of postsynaptic potentials evoked at different depths. The model successfully reproduced the progressive spike amplitude reduction as a function of stimulation depth, as well as the effects of chloride and cesium. The model revealed that somatic spikes contain an important contribution from proximal dendritic sodium currents up to ]100 µm and ]300 µm from the soma under control and cesium conditions, respectively. Proximal inhibitory postsynaptic potentials can prevent this dendritic participation thus reducing the spike amplitude at the soma. The model suggests that the somatic spike amplitude and shape can be used as a ''window'' to infer the electrical participation of proximal dendrites.Thus, our results suggest that inhibitory postsynaptic potentials can control the participation of proximal dendrites in somatic sodium spikes.1998 IBRO. Published by Elsevier Science Ltd.Key words: multicompartment models, intrinsic electrophysiological properties, in vivo intracellular recordings, action potentials, dendritic integration.By comparing the shape of antidromic, orthodromic and current-evoked action potentials (APs) in motoneurons, Coombs et al. 7 provided compelling evidence for the idea that APs are initiated at the initial segment (IS) and then invade the somatodendritic compartment. However, the applicability of this model to other cell types was questioned when the first intradendritic recordings revealed that dendrites can sustain active electrogenesis. 33,34,63 In neocortical and hippocampal pyramidal neurons for instance, intracellular recordings revealed that dendritic spikes can be elicited by synaptic inputs 5,9,30,52 and that they can amplify synaptic inputs electrotonically distant from the soma to initiate APs. 5 Moreover, the prox...

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confidence: 99%

Inhibitory control of somatodendritic interactions underlying action potentials in neocortical pyramidal neurons in vivo: An intracellular and computational study

Paré¹,

Lang²,

Destexhe³

1998

Neuroscience

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“…[ NMDA receptors mediate synaptic transmission and neural plasticity at many sites in the mammalian CNS (Mayer and Westbrook, 1987;Collingridge and Lester, 1989; and also contribute to epileptiform activity and neuronal cell death in a number of experimental and pathological conditions Greenamyre and Young, 1989;Meldrum and Garthwaite, 1990). The identification and molecular characterization of functionally distinct NMDA receptor subtypes will contribute to a better understanding of the specific role of these receptors in many normal and pathological conditions.…”

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The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition

et al. 1994

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The relationship between four pharmacologically distinct NMDA receptor subtypes, identified in radioligand binding studies, and the recently identified NMDA receptor subunits (NR1a-g, NR2A-D) has not been determined. In this report, we demonstrate that the anatomical distribution of the four NMDA receptor subtypes strikingly parallels the distribution of mRNA encoding NR2A-D subunits. The distribution of NR2A mRNA was very similar to that of “antagonist-preferring” NMDA receptors [defined by high-affinity 3H-2-carboxypiperazine-4-yl-propyl- 1-phosphonic (3H-CPP) binding sites; correlation coefficient = 0.88]. Agonist-preferring NMDA receptors localized to brain regions expressing both NR2B mRNA and NR1- mRNA (NR1 splice variant lacking insert 1). NR2C mRNA was largely restricted to the cerebellar granule cell layer, a region that displays a unique pharmacological profile. NR2D mRNA localized exclusively to those diencephalic nuclei that have a fourth, distinct pharmacological profile (typified by the midline thalamic nuclei). The pharmacology of native NMDA receptors was compared to that of heteromeric NMDA receptors expressed in Xenopus oocytes (NR1/NR2A, NR1/NR2B, NR1/NR2C). The oocyte-expressed NR1/NR2A receptor displayed a higher affinity for antagonists and a slightly lower affinity for agonists than the NR1/NR2B receptor. These patterns are analogous to those found for radioligand binding to native receptors in the lateral thalamus and medial striatum, respectively. NMDA receptors in the lateral thalamus (with a high density of NR2A subunit mRNA) displayed higher affinity for antagonists and a lower affinity for agonists than did NMDA receptors of the medial striatum (a region rich in NR2B mRNA). Relative to the NR1/NR2A and NR1/NR2B receptors, oocyte-expressed NR1/NR2C receptors had a lower affinity specifically for both D-3-(2- carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid (D-CPPene) and homoquinolinate (HQ). This pattern was identical to that observed for cerebellar (NR2C-containing) versus forebrain (NR2A- and NR2B- containing) NMDA receptors. Taken together, the data in this report suggest that the four previously identified native NMDA receptor subtypes differ in their NR2 composition. Furthermore, the NR2 subunits significantly contribute to the anatomical and pharmacological diversity of NMDA receptor subtypes.

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“…Our analyses suggest that the apparent glycine affinity increases by about 3.7 times in Ca-containing solution. Glutamate and aspartate are the major excitatory transmitters participating in the synaptic transmission in the CNS, including medullary and spinal dorsal horns (Jahr and Jessell, 1985;Mayer and Westbrook, 1987b;Gu and Huang, 1989;Murase et al, 1989;Yoshimura and Jessell, 1990;Chen and Huang, 1991). The NMDA receptor channel is one of the postsynaptic targets for these excitatory amino acids (Mayer and Westbrook, 1987b).…”

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Modulation of glycine affinity for NMDA receptors by extracellular Ca2+ in trigeminal neurons

Huang

1994

J. Neurosci.

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Glycine and the divalent cation Ca2+ play key roles in regulating the activity of excitatory amino acid NMDA receptor channels. There is accumulating evidence that the concentration of glycine at the synaptic cleft is below a saturated level. We examined the effect of external Ca2+ on NMDA responses in various concentrations of glycine in isolated trigeminal neurons. We found that external Ca2+ potentiated NMDA responses and this potentiation occurred only when glycine sites were unsaturated. Since single-channel conductance decreases in the high external Ca2+ solution, the observation cannot be explained by an increase in Ca2+ influx through the channels. Studying the dose- response curves for glycine in different Ca2+ solutions, we found that the apparent dissociation constant (EC50) for glycine decreases with increasing external Ca2+ concentrations. Kinetics studies of glycine binding to NMDA receptors indicated that external Ca2+ causes a decrease in the off rate of the glycine binding, while having no effect on the on rate. Our analyses suggest that the apparent glycine affinity increases by about 3.7 times in Ca-containing solution. Thus, external Ca2+ contributes to the unusually high glycine affinity for NMDA receptors and may have a role in regulating the NMDA receptor channel activities during intensive or sustained neuronal stimulation.

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The physiology of excitatory amino acids in the vertebrate central nervous system

Cited by 1,656 publications

References 367 publications

Inhibitory control of somatodendritic interactions underlying action potentials in neocortical pyramidal neurons in vivo: An intracellular and computational study

Inhibitory control of somatodendritic interactions underlying action potentials in neocortical pyramidal neurons in vivo: An intracellular and computational study

The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition

Modulation of glycine affinity for NMDA receptors by extracellular Ca2+ in trigeminal neurons

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