In the Developing Rat Hippocampus, Endogenous Activation of Presynaptic Kainate Receptors Reduces GABA Release from Mossy Fiber Terminals

Caiati, Maddalena D.; Sivakumaran, Sudhir; Cherubini, Enrico

doi:10.1523/jneurosci.4566-09.2010

Cited by 25 publications

(21 citation statements)

References 76 publications

(131 reference statements)

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“…Activity‐dependent downregulation of the tonic KAR activity during maturation of presynaptic properties involves BDNF‐TrkB signalling (Sallert et al ., ). Similarly, tonic activation of presynaptic GluK1‐containing KARs markedly depresses neonate mossy fibre synapses, which operate mostly with GABA as a neurotransmitter (Caiati et al ., ). Moreover, presynaptic GluK1‐containing KARs present on mossy fibre terminals account for the persistent depression of GABAergic transmission at neonate synapses observed after pairing presynaptic mossy fibre stimulation with postsynaptic spiking (Caiati et al ., ).…”

Section: Role Of Kars In the Developing Hippocampusmentioning

confidence: 97%

“…Similarly, tonic activation of presynaptic GluK1‐containing KARs markedly depresses neonate mossy fibre synapses, which operate mostly with GABA as a neurotransmitter (Caiati et al ., ). Moreover, presynaptic GluK1‐containing KARs present on mossy fibre terminals account for the persistent depression of GABAergic transmission at neonate synapses observed after pairing presynaptic mossy fibre stimulation with postsynaptic spiking (Caiati et al ., ). Overall, tonic activation of presynaptic KARs in the neonate limits the activation of excitatory connections, being GABA‐depolarising at this stage.…”

Section: Role Of Kars In the Developing Hippocampusmentioning

confidence: 97%

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Kainate receptors in the hippocampus

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Fièvre

Gorlewicz

et al. 2014

Eur J of Neuroscience

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Kainate receptors (KARs) consist of a family of ionotropic glutamate receptors composed of the combinations of five subunits, GluK1-GluK5. Although KARs display close structural homology with AMPA receptors, they serve quite distinct functions. A great deal of our knowledge of the molecular and functional properties of KARs comes from their study in the hippocampus. This review aims at summarising the functions of KARs in the regulation of the activity of hippocampal synaptic circuits at the adult stage and throughout development. We focus on the variety of roles played by KARs in physiological conditions of activation, at pre- and postsynaptic sites, in different cell types and through either metabotropic or ionotropic actions. Finally, we present some of the few attempts to link the role of KARs in the regulation of local hippocampal circuits to the behavioural functions of the hippocampus in health and diseases.

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Section: Role Of Kars In the Developing Hippocampusmentioning

confidence: 97%

Section: Role Of Kars In the Developing Hippocampusmentioning

confidence: 97%

Kainate receptors in the hippocampus

Carta

Fièvre

Gorlewicz

et al. 2014

Eur J of Neuroscience

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“…Hippocampal slices were obtained from at postnatal (P) days P2-P6 (day 0 was considered the day of birth) animals using a standard protocol (Caiati et al, 2010). Briefly, the brain was quickly removed from the skull and placed in ice-cold ACSF containing (in mM): NaCl 130, KCl 3.5, NaH 2 PO 4 1.2, MgCl 2 1.3, CaCl 2 2, Glucose 24, NaHCO 3 27, saturated with 95% O 2 and 5% CO 2 (pH 7.3–7.4).…”

Section: Methodsmentioning

confidence: 99%

Fluoxetine impairs GABAergic signaling in hippocampal slices from neonatal rats

Caiati¹,

Cherubini²

2013

Front. Cell. Neurosci.

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Fluoxetine (Prozac), an antidepressant known to selectively inhibit serotonin reuptake, is widely used to treat mood disorders in women suffering from depression during pregnancy and postpartum period. Several lines of evidence suggest that this drug, which crosses the human placenta and is secreted into milk during lactation, exerts its action not only by interfering with serotoninergic but also with GABAergic transmission. GABA is known to play a crucial role in the construction of neuronal circuits early in postnatal development. The immature hippocampus is characterized by an early type of network activity, the so-called Giant Depolarizing Potentials (GDPs), generated by the synergistic action of glutamate and GABA, both depolarizing and excitatory. Here we tested the hypothesis that fluoxetine may interfere with GABAergic signaling during the first postnatal week, thus producing harmful effects on brain development. At micromolar concentrations fluoxetine severely depressed GDPs frequency (IC50 22 μM) in a reversible manner and independently of its action on serotonin reuptake. This effect was dependent on a reduced GABAergic (but not glutamatergic) drive to principal cells most probably from parvalbumin-positive fast spiking neurons. Cholecystokinin-positive GABAergic interneurons were not involved since the effects of the drug persisted when cannabinoid receptors were occluded with WIN55,212-2, a CB1/CB2 receptor agonist. Fluoxetine effects on GABAergic transmission were associated with a reduced firing rate of both principal cells and interneurons further suggesting that changes in network excitability account for GDPs disruption. This may have critical consequences on the functional organization and stabilization of neuronal circuits early in postnatal development.

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“…Presynaptic KARs can bidirectionally modulate neurotransmitter release, both at glutamatergic and GABAergic synapses. The inhibitory but not the facilitatory activity of KARs is most likely linked to G‐protein coupled mechanisms 8,14,19,25,34,41,45,46,61,62. The inhibition of voltage‐gated Ca 2+ ‐channels by KARs through G i/o ‐protein and PKC activation, independent of ion flux,11 may contribute to the inhibitory action of KARs on neurotransmitter release.…”

Section: Introductionmentioning

confidence: 99%

Metabotropic signaling by kainate receptors

Rodrigues

Lerma

2012

WIREs Membr Transp Signal

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Kainate receptors (KARs) are members of the ionotropic glutamate receptor family. Despite their ubiquitous presence in the central nervous system, and in contrast to the better characterized N-methyl-D-aspartates (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), the contribution of KARs to synaptic transmission has only been demonstrated in a few central synapses. However, there is now accumulating evidence that KARs are present on both sides of the synapse, where they play distinct and diverse roles. In addition to their contribution to synaptic transmission, KARs can regulate synaptic activity and plasticity either by presynaptically modulating neurotransmitter release at GABAergic and glutamatergic synapses, or by postsynaptically regulating neuronal excitability. This prominent neuromodulatory role of KARs has been further highlighted by the finding that these glutamate-gated ion-channels can also signal through G-proteins and other second messengers. This noncanonical metabotropic signaling of KARs was firmly established by demonstrating it to be independent of ion flux. The discovery of this dual signaling capacity of KARs constituted a breakthrough in understanding how they function and since then, an increasing number of metabotropic actions of KARs have been reported. It is now clear that this dual signaling underlies the diverse functions of KARs and defining this metabotropic component of the signaling system operated by KARs will be necessary to understand the physiological contributions of glutamate receptors.

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In the Developing Rat Hippocampus, Endogenous Activation of Presynaptic Kainate Receptors Reduces GABA Release from Mossy Fiber Terminals

Cited by 25 publications

References 76 publications

Kainate receptors in the hippocampus

Kainate receptors in the hippocampus

Fluoxetine impairs GABAergic signaling in hippocampal slices from neonatal rats

Metabotropic signaling by kainate receptors

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