Outwardly Rectifying Tonically Active GABA<sub>A</sub>Receptors in Pyramidal Cells Modulate Neuronal Offset, Not Gain

Pavlov, Ivan; Savtchenko, Leonid P.; Kullmann, Dimitri M.; Semyanov, Alexey; Walker, Matthew C.

doi:10.1523/jneurosci.2747-09.2009

Cited by 112 publications

(137 citation statements)

References 60 publications

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“…The amplitude of the eGABA A R-mediated tonic current does not remain constant over time, but fluctuates in relation to the ambient GABA concentration (Pavlov et al 2009). Moreover, eGABA A Rs are dynamic entities showing plasticity in response to changes in sGABA A Rs activity (Nani et al 2013) and modulation by exogenous agents including neurosteroids, alcohol and anesthestetics (see Chap.…”

Section: Discussionmentioning

confidence: 99%

GPCR Modulation of Extrasynapitic GABAA Receptors

Connelly

Errington

Yagüe

et al. 2014

Extrasynaptic GABAA Receptors

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γ-Aminobutyric acid type A (GABA A ) receptors (GABA A Rs), the main inhibitory neurotransmitter-gated ion channels in the central nervous system, are finely tuned by other neurotransmitters and endogenous ligands. The regulation of synaptic GABA A Rs (sGABA A Rs) by G protein-coupled receptors (GPCRs) has been well characterized and is known to occur either through the conventional activation of second-messenger signalling cascades by G proteins or directly by protein-protein coupling. In contrast, research on the modulation of extrasynaptic GABA A R (eGABA A Rs) is still in its infancy and it remains to be determined whether both of the above mechanisms are capable of controlling eGABA A R function. In this chapter, we summarize the available literature on eGABA A R modulation by GPCRs, including GABA B , serotonin (5-HT), dopamine (DA), noradrenaline (NA) and metabotropic glutamate (mGlu) receptors. Although at present these GPCRs-eGABA A Rs cross-talks have been investigated in a limited number of brain areas (i.e., thalamus, cerebellum, hippocampus, striatum), it is already evident that eGABA A Rs show a nucleus-and neuronal type-selective regulation by GPCRs that differs from that of sGABA A Rs. This distinct regulation of eGABA A Rs versus sGABA A Rs by GPCRs provides mechanisms for receptor adaptation in response

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Section: Discussionmentioning

confidence: 99%

GPCR Modulation of Extrasynapitic GABAA Receptors

Connelly

Errington

Yagüe

et al. 2014

Extrasynaptic GABAA Receptors

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“…In addition, the reduction in input resistance could attenuate the influence of excitatory glutamatergic inhibition through a shunting mechanism (Mitchell and Silver, 2003). In hippocampal pyramidal neurons, the tonic conductance has been shown to alter the input-output function predominantly by altering neuronal excitability at spiking threshold (Pavlov et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

α5GABA_AReceptor Activity Sets the Threshold for Long-Term Potentiation and Constrains Hippocampus-Dependent Memory

Martin¹,

Zurek²,

MacDonald³

et al. 2010

J. Neurosci.

164

138

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Synaptic plasticity, which is the neuronal substrate for many forms of hippocampus-dependent learning, is attenuated by GABA type A receptor (GABA A R)-mediated inhibition. The prevailing notion is that a synaptic or phasic form of GABAergic inhibition regulates synaptic plasticity; however, little is known about the role of GABA A R subtypes that generate a tonic or persistent inhibitory conductance. We studied the regulation of synaptic plasticity by ␣5 subunit-containing GABA A Rs (␣5GABA A Rs), which generate a tonic inhibitory conductance in CA1 pyramidal neurons using electrophysiological recordings of field and whole-cell potentials in hippocampal slices from both wild-type and null mutant mice for the ␣5 subunit of the GABA A R (Gabra5 ؊/؊ mice). In addition, the strength of fearassociated memory was studied. The results showed that ␣5GABA A R activity raises the threshold for induction of long-term potentiation in a highly specific band of stimulation frequencies (10 -20 Hz) through mechanisms that are predominantly independent of inhibitory synaptic transmission. The deletion or pharmacological inhibition of ␣5GABA A Rs caused no change in baseline membrane potential or input resistance but increased depolarization during 10 Hz stimulation. The encoding of hippocampus-dependent memory was regulated by ␣5GABA A Rs but only under specific conditions that generate moderate but not robust forms of fear-associated learning. Thus, under specific conditions, ␣5GABA A R activity predominates over synaptic inhibition in modifying the strength of both synaptic plasticity in vitro and certain forms of memory in vivo.

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“…Tonic inhibition is also an important GABAA receptor-mediated inhibition that modulates neuronal gain [47] and offset [48], and thus controls neuronal output patterns and synaptic integration [49]. These modulations would be important in visual feature processing, but the properties of tonic inhibition in the visual cortex have not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

The Development of Phasic and Tonic Inhibition in the Rat Visual Cortex

Jang

Cho

Park

et al. 2010

Korean J Physiol Pharmacol

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Gamma-aminobutyric acid (GABA)-ergic inhibition is important in the function of the visual cortex.In a previous study, we reported a developmental increase in GABAA receptor-mediated inhibition in the rat visual cortex from 3 to 5 weeks of age. Because this developmental increase is crucial to the regulation of the induction of long-term synaptic plasticity, in the present study we investigated in detail the postnatal development of phasic and tonic inhibition. The amplitude of phasic inhibition evoked by electrical stimulation increased during development from 3 to 8 weeks of age, and the peak time and decay kinetics of inhibitory postsynaptic potential (IPSP) and current (IPSC) slowed progressively. Since the membrane time constant decreased during this period, passive membrane properties might not be involved in the kinetic changes of IPSP and IPSC. Tonic inhibition, another mode of GABAA receptor-mediated inhibition, also increased developmentally and reached a plateau at 5 weeks of age. These results indicate that the time course of the postnatal development of GABAergic inhibition matched well that of the functional maturation of the visual cortex. Thus, the present study provides significant insight into the roles of inhibitory development in the functional maturation of the visual cortical circuits.

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Outwardly Rectifying Tonically Active GABA_AReceptors in Pyramidal Cells Modulate Neuronal Offset, Not Gain

Cited by 112 publications

References 60 publications

GPCR Modulation of Extrasynapitic GABAA Receptors

GPCR Modulation of Extrasynapitic GABAA Receptors

α5GABA_AReceptor Activity Sets the Threshold for Long-Term Potentiation and Constrains Hippocampus-Dependent Memory

The Development of Phasic and Tonic Inhibition in the Rat Visual Cortex

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Outwardly Rectifying Tonically Active GABAAReceptors in Pyramidal Cells Modulate Neuronal Offset, Not Gain

Cited by 112 publications

References 60 publications

GPCR Modulation of Extrasynapitic GABAA Receptors

GPCR Modulation of Extrasynapitic GABAA Receptors

α5GABAAReceptor Activity Sets the Threshold for Long-Term Potentiation and Constrains Hippocampus-Dependent Memory

The Development of Phasic and Tonic Inhibition in the Rat Visual Cortex

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Outwardly Rectifying Tonically Active GABA_AReceptors in Pyramidal Cells Modulate Neuronal Offset, Not Gain

α5GABA_AReceptor Activity Sets the Threshold for Long-Term Potentiation and Constrains Hippocampus-Dependent Memory