The Ionic Mechanisms of Excitatory and Inhibitory Synaptic Action

Eccles, John C.

doi:10.1111/j.1749-6632.1966.tb50176.x

Cited by 57 publications

(25 citation statements)

References 41 publications

(29 reference statements)

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“…GABAergic neurons also control the generation of behaviorally relevant patterns and oscillations that may turn out to be far more important than inhibition per se. In addition, GABA depolarizes neurons because of a "reversed" chloride gradient in a wide range of neuron types and animal species, notably invertebrates (82,163,177,178,182,229,285,355,356,674). Even in adult mammalian cortical neurons, dendritic GABAergic action is depolarizing because of a locally reversed Cl Ϫ gradient and not a different ionic mechanism, as was thought for some years (14; also see Refs.…”

Section: Introduction and Historical Perspectivesmentioning

confidence: 87%

“…As such, GABAergic signaling plays a major role in brain physiology, and dysfunction of GABAergic signaling can result in pathological conditions such as epilepsies that are generated when the balance between excitation and inhibition is impaired (16,178,179,181,284,(525)(526)(527). Recent studies suggest a more complex scope of functions for GABAergic signaling than just global inhibition.…”

Section: Introduction and Historical Perspectivesmentioning

confidence: 99%

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GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations

Ben-Ari

Gaı̈arsa

Tyzio

et al. 2007

Physiological Reviews

1,143

1,123

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Developing networks follow common rules to shift from silent cells to coactive networks that operate via thousands of synapses. This review deals with some of these rules and in particular those concerning the crucial role of the neurotransmitter γ-aminobuytric acid (GABA), which operates primarily via chloride-permeable GABAAreceptor channels. In all developing animal species and brain structures investigated, neurons have a higher intracellular chloride concentration at an early stage leading to an efflux of chloride and excitatory actions of GABA in immature neurons. This triggers sodium spikes, activates voltage-gated calcium channels, and acts in synergy with NMDA channels by removing the voltage-dependent magnesium block. GABA signaling is also established before glutamatergic transmission, suggesting that GABA is the principal excitatory transmitter during early development. In fact, even before synapse formation, GABA signaling can modulate the cell cycle and migration. The consequence of these rules is that developing networks generate primitive patterns of network activity, notably the giant depolarizing potentials (GDPs), largely through the excitatory actions of GABA and its synergistic interactions with glutamate signaling. These early types of network activity are likely required for neurons to fire together and thus to “wire together” so that functional units within cortical networks are formed. In addition, depolarizing GABA has a strong impact on synaptic plasticity and pathological insults, notably seizures of the immature brain. In conclusion, it is suggested that an evolutionary preserved role for excitatory GABA in immature cells provides an important mechanism in the formation of synapses and activity in neuronal networks.

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Section: Introduction and Historical Perspectivesmentioning

confidence: 87%

Section: Introduction and Historical Perspectivesmentioning

confidence: 99%

GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations

Ben-Ari

Gaı̈arsa

Tyzio

et al. 2007

Physiological Reviews

1,143

1,123

View full text Add to dashboard Cite

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“…Activation of these receptors increases a Cl Ϫ conductance, which in the majority of mature neurons results in Cl Ϫ influx and thus in hyperpolarization (Eccles, 1966;Krnjevic, 1974). The basis of the Cl Ϫ influx is a relatively low intracellular free Cl Ϫ concentration ([Cl Ϫ ] i ), leading to an inward-directed electrochemical gradient for Cl Ϫ at the resting membrane potential (V rest ).…”

Section: Introductionmentioning

confidence: 99%

Expression and Function of Chloride Transporters during Development of Inhibitory Neurotransmission in the Auditory Brainstem

et al. 2003

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“…Whereas in the above examples the inhibitory potentials seem to be due to a change in permeability to either potassium or chloride, in some preparations (certain molluscan neurones, Kerkut & Thomas, 1964; crayfish stretch receptor neurone, Edwards & Hagiwara, 1959; Hagiwara, Kusano & Saito, 1960;motoneurones, see Eccles, 1966;guinea-pig 87 Biilbring & Tomita, 1969), the transmitter has been assumed to increase both potassium and chloride permeabilities. In all of these cases, however, the experimental evidence has shown that one of the two ions plays the major role, and the data pointing to a contribution by the second ion are sometimes either indirect or insufficient.…”

Section: Introductionmentioning

confidence: 99%

Ionic mechanism of a two‐component cholinergic inhibition in Aplysia neurones

Kehoe¹

1972

The Journal of Physiology

218

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1. A two‐component inhibition, consisting of a rapid and slow i.p.s.p., has been observed in the medial cells of the pleural ganglion of Aplysia. Each i.p.s.p. has been shown to be mediated by a distinct cholinergic receptor. The ionic mechanisms of the two components of the inhibitory response (whether elicited synaptically or by ACh injection) are analysed in this paper. 2. The inversion potential (typically −60 mV) of the rapid i.p.s.p. and of the rapid response to ACh injection is selectively altered by an intracellular injection of chloride or by partial substitution of the external chloride by impermeant anions. The shift caused by this last procedure is similar to that predicted for the chloride equilibrium potential (ECl) by the Nernst equation. 3. The slow i.p.s.p. and the slow response to ACh injection (both of which invert around −80 mV) are insensitive to changes in either internal or external chloride concentrations; on the contrary, with alterations of the concentration of potassium in the external medium, the inversion potential of the slow responses is altered in a way similar to that expected for the potassium equilibrium potential (EK). 4. It is concluded that the rapid i.p.s.p. and the corresponding ACh potential are due to a change in chloride permeability of the post‐synaptic membrane, whereas the slow responses are due to a selective change in potassium permeability. 5. Additional data suggest that the fast, ‘chloride’ channel is impermeable to sulphate and methylsulphate, but slightly permeable to propionate and isethionate. The slow, ‘potassium’ channel is impermeable to caesium ions, whereas its permeability to rubidium ions is half that to potassium. 6. The potassium permeability of both the non‐synaptic and synaptic membrane is markedly reduced by an intracellular injection of either tetraethylammonium (TEA) or caesium. These ions not only block the cholinergic potassium currents (whether inward or outward) but likewise block the potassium currents activated in the same cells by an iontophoretic injection of dopamine. 7. The potassium dependent synaptic potentials are also selectively affected by manipulations known to block the electrogenic sodium pump. In the presence of ouabain or in sea water in which sodium has been replaced by lithium, there is an apparent reduction of these potentials which was shown to be simply a reflexion of the movement of EK towards a less polarized level. This shift in inversion potential was not seen for the potassium dependent response to ACh iontophoretic injection. These results are interpreted in terms of accumulation of potassium ions assumed to occur in the extracellular spaces of the neuropile, but not in the thoroughly dissected somatic region. 8. Cooling was shown to eliminate, selectively, the synaptic and ACh potential changes caused by an increase in potassium permeability.

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The Ionic Mechanisms of Excitatory and Inhibitory Synaptic Action

Cited by 57 publications

References 41 publications

GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations

GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations

Expression and Function of Chloride Transporters during Development of Inhibitory Neurotransmission in the Auditory Brainstem

Ionic mechanism of a two‐component cholinergic inhibition in Aplysia neurones

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