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Review
. 2005 Jan;87(1):3-16.
doi: 10.1016/j.pbiomolbio.2004.06.001.

Tonic excitation and inhibition of neurons: ambient transmitter sources and computational consequences

Pauline Cavelier  1 , Martine Hamann, David Rossi, Peter Mobbs, David Attwell
Affiliations
Review

Tonic excitation and inhibition of neurons: ambient transmitter sources and computational consequences

Pauline Cavelier et al. Prog Biophys Mol Biol. 2005 Jan.

Abstract

Tonic activation of excitatory and inhibitory receptors, by the ambient concentration of neurotransmitters in the extracellular space of the brain, has been suggested to underlie phenomena as diverse as relapse to cocaine use by reward pathways in the striatum, sparse coding of motor information in the cerebellum, and control of the development of the cerebral and cerebellar cortices. Here we assess the mechanisms which may determine the ambient levels of excitatory and inhibitory neurotransmitters, and consider their likely effect on information processing.

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Figures

Fig. 1.
Fig. 1.
The effect of a non-zero baseline extracellular glutamate concentration on the activation of NMDA receptors. Continuous curve is the activation curve for NMDA receptors (, with EC50 = 2.3 μM, from Patneau and Mayer, 1990). Na+-dependent transporters with the stoichiometry measured for EAAC1 and GLT-1 can theoretically lower [glu]o to ~2 nM (left arrow). Microdialysis experiments typically measure a resting [glu]o of ~2 μM (right arrow), which is sufficient to activate NMDA receptors by 45% of their maximum activation, so that subsequent rises of [glu]o produce a smaller change of activation than would occur with no glutamate present initially. Prolonged presence of glutamate also desensitises NMDA receptors. The dashed line, given by I/Imax=[IC501.5/([glu]o1.5+IC501.5), with IC50=1.3 μM, shows the inhibition of the NMDA component of EPSCs measured by Zorumski et al. (1996): this curve overestimates the amount of desensitization occurring, because pre-synaptic actions of glutamate contribute a small amount to the EPSC depression (e.g. at 1 μM glutamate, presynaptic inhibition alone inhibits the response by about 12% while the combination of pre-synaptic inhibition and desensitization inhibits by about 42%: see Zorumski et al. (1996) Fig. 6B).
Fig. 2.
Fig. 2.
The effect of tonic inhibition of cerebellar granule cells on information transfer through the cerebellar cortex of rats (from the study of Hamann et al., 2002). (A) Granule cell firing rate (normalised to maximum rate in nine cells) as a function of injected current, in control conditions and with tonic inhibition by high affinity GABAA receptors blocked with furosemide. The input–output curve is shifted to the left by blocking the tonic inhibition. (B) Granule cell firing rate (normalized to maximum rate in four cells) as a function of mossy fibre stimulation rate, in the presence and absence (furosemide) of tonic inhibition. (C) Purkinje cell firing rate as a function of mossy fibre stimulation rate, in the presence and absence (furosemide) of tonic inhibition.
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