Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells

Newberry, Nigel R.; Nicoll, Roger A.

doi:10.1038/308450a0

Cited by 324 publications

(116 citation statements)

References 25 publications

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“…In subsequent experiments, slices were perfused with the GABA B receptor agonist, baclofen, which inhibited PS amplitude by reducing GluR-mediated excitatory synaptic transmission. These data are in agreement with previous findings that GABA-BR activation inhibits excitatory synaptic transmission by presynaptic inhibition of glutamate release (Davies et al, 1993;Isaacson et al, 1993;Ziakopoulos et al, 2000), as well as postsynaptic hyperpolarization of CA1 cells (Newberry and Nicoll, 1984). In these experiments, no difference between control and MβCD-treated slices was observed.…”

Section: Cyclodextrine Effects On Synaptic Transmission In Hippocampasupporting

confidence: 83%

Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus

Frank

Rufini

Tancredi

et al. 2008

Experimental Neurology

115

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Several neurodegenerative disorders are associated with impaired cholesterol homeostasis in the nervous system where cholesterol is known to play a role in modulating synaptic activity and stabilizing membrane microdomains. In the present report, we investigated the effects of methyl-β-cyclodextrin-induced cholesterol depletion on synaptic transmission and on the expression of 1) paired-pulse facilitation (PPF); 2) paired-pulse inhibition (PPI) and 3) long-term potentiation (LTP) in the CA1 hippocampal region. Results demonstrated that cyclodextrin strongly reduced synaptic transmission and blocked the expression of LTP, but did not affect PPF and PPI. The role of glutamatergic and GABAergic receptors in these cholesterol depletion-mediated effects was evaluated pharmacologically. Data indicate that, in cholesterol depleted neurons, modulation of synaptic transmission and synaptic plasticity phenomena are sustained by AMPA-, kainate-and NMDA-receptors but not by GABA-receptors. The involvement of AMPA-and kainate-receptors was confirmed by fluorimetric analysis of intracellular calcium concentrations in hippocampal cell cultures. These data suggest that modulation of receptor activity by manipulation of membrane lipids is a possible therapeutic strategy in neurodegenerative disease.

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Section: Cyclodextrine Effects On Synaptic Transmission In Hippocampasupporting

confidence: 83%

Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus

Frank

Rufini

Tancredi

et al. 2008

Experimental Neurology

115

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“…Thus, GABA B receptormediated synaptic transmission was inhibited by nociceptin receptor activation; however, this finding is inconsistent with the decreased excitability of pyramidal cells caused by nociceptin (Fig. 2) because GABA B receptor-mediated synaptic transmission should hyperpolarize pyramidal cells through an increase in the K ϩ -channel conductance (Newberry and Nicoll, 1984;Dutar and Nicoll, 1988a), and the reduction of GABA B -IPSCs should increase the excitability of pyramidal cells. Therefore, GABA B receptor-mediated synaptic transmission should not play a significant role in the LTP modulation via the nociceptin system.…”

Section: Modulation Of Inhibitory Synaptic Transmission By Nociceptinmentioning

confidence: 40%

The Neuropeptide Nociceptin Is a Synaptically Released Endogenous Inhibitor of Hippocampal Long-Term Potentiation

Bongsebandhu-phubhakdi

Manabe²

2007

J. Neurosci.

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Hippocampal long-term potentiation (LTP) of excitatory synaptic transmission has been regarded as a cellular model of learning and memory. Its induction is regulated by many functional molecules at synapses, including the neuropeptide nociceptin, which is identified as an endogenous ligand for the orphan opioid receptor. Mutant mice lacking the receptor exhibit enhanced LTP and hippocampusdependent memory formation; however, the precise molecular and cellular mechanism is largely unknown. Here, we show that LTP in the hippocampal CA1 region is inhibited by nociceptin synaptically released from interneurons by tetanic stimulation. This endogenous nociceptin downregulates the excitability of pyramidal cells by the hyperpolarization induced by the activation of K ϩ channels, which are the common target shared with GABA B receptors, although the mode of action is considerably different. Interestingly, the modulation of LTP by endogenous nociceptin is not observed when theta-burst stimulation is used instead of tetanic stimulation, suggesting that relatively longer high-frequency synaptic activation is required for the release of endogenous nociceptin. These results indicate that, in addition to GABA, nociceptin released from interneurons by their high-frequency activation is a novel endogenous neuromodulator that negatively regulates LTP induction in the hippocampus through direct modulation of pyramidal cells.

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“…This protocol has been used in other studies to activate the G-protein coupled inwardly rectifying potassium channels that underlie the slow GABA B IPSCs recorded in Figure 3A (Newberry and Nicoll, 1984;Gahwiler and Brown, 1985;Sodickson and Bean, 1996;Liu and Leung, 2003). Under our recording conditions, bath application of 20 M baclofen induced an outward current of 76.1 Ϯ 14.8 pA (n ϭ 5) (Fig 3B).…”

Section: Ethanol Increases Presynaptic Gaba B Receptor Activitymentioning

confidence: 88%

Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABA_BReceptors

Ariwodola

Weiner²

2004

J. Neurosci.

142

137

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Ethanol enhances GABAergic synaptic inhibition, and this interaction contributes to many of the behavioral and cognitive effects of this drug. Most studies suggest that ethanol enhances GABAergic neurotransmission via an allosteric potentiation of the postsynaptic GABA A receptors that mediate fast synaptic inhibition in the mammalian CNS. Despite widespread acceptance of this hypothesis, direct support for such a mechanism has been difficult to obtain. Ethanol does not enhance GABA A receptor function in all brain regions or under all experimental conditions, and factors responsible for this variability remain mostly unknown. Notably, blockade of GABA B receptors dramatically enhances ethanol potentiation of hippocampal GABA A IPSPs and IPSCs, suggesting that some unknown GABA B receptor mechanism limits the overall potentiating effect of ethanol on GABAergic synapses. In this study, we demonstrate that, at perisomatic synapses in the rat hippocampus, ethanol enhances presynaptic GABA B autoreceptor function and that this interaction reduces the overall potentiating effect of ethanol at these synapses. We further show that ethanol significantly elevates basal presynaptic GABA B receptor tone, possibly via an increase in spontaneous GABA release, and that pretreatment with a subthreshold concentration of the GABA B receptor agonist baclofen blocks ethanol but not flunitrazepam or pentobarbital potentiation of GABA A IPSCs. These data suggest that an interaction between ethanol and presynaptic GABA B autoreceptor activity regulates the ethanol sensitivity of GABAergic synapses. Given that the in vitro ethanol sensitivity of these synapses correlates with in vivo ethanol responsiveness in a number of rodent lines, our data further suggest that presynaptic GABA B receptor activity may play a role in regulating behavioral sensitivity to ethanol.

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Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells

Cited by 324 publications

References 25 publications

Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus

Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus

The Neuropeptide Nociceptin Is a Synaptically Released Endogenous Inhibitor of Hippocampal Long-Term Potentiation

Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABA_BReceptors

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Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells

Cited by 324 publications

References 25 publications

Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus

Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus

The Neuropeptide Nociceptin Is a Synaptically Released Endogenous Inhibitor of Hippocampal Long-Term Potentiation

Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABABReceptors

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Ethanol Potentiation of GABAergic Synaptic Transmission May Be Self-Limiting: Role of Presynaptic GABA_BReceptors