LTP of GABAergic synapses in the ventral tegmental area and beyond

Nugent, Fereshteh S.; Kauer, Julie A.

doi:10.1113/jphysiol.2007.148098

Cited by 72 publications

(57 citation statements)

References 64 publications

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“…If inhibitory interneurons that maintained a strong inhibitory drive over DA neurons express GluN2A, blockade of these receptors would then allow DA neurons to pass from a silent state into a tonic firing state; this state will increase the probability that a glutamate signal initiates burst firing. Glutamate participates in this form of feedforward inhibition, altering the plasticity of local inhibitory neurons and dopamine cell firing as in-vitro electrophysiological recordings had shown (Bonci and Malenka, 1999;Nugent and Kauer, 2008). But how can we explain the fact that VM microinjection of PPPA, a preferred GluN2A antagonist, still enhanced reward in animals that had a reduction in NMDARs, and particularly in GluN2A subunits?…”

Section: Discussionmentioning

confidence: 99%

Reduction in Ventral Midbrain NMDA Receptors Reveals Two Opposite Modulatory Roles for Glutamate on Reward

Hernández

Khodami-Pour

Lévesque

et al. 2015

Neuropsychopharmacol

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Glutamate is a major component of the reward circuitry and recent clinical studies suggest that new molecules that would target glutamate neurotransmission are most likely to constitute more effective medications for mood disorders. It is well known that activation of N-methyl-D-aspartate glutamate receptors (NMDARs) initiates dopamine burst firing, a mode associated with reward signaling; but NMDARs also contribute to the maintenance of an inhibitory drive to dopamine neurons. Such opposite modulatory functions imply that different subtypes of NMDARs are expressed on different ventral midbrain (VM) neurons and/or afferent inputs to dopamine neurons. By using the small interfering RNA (siRNA) technique, we studied the effects of VM downregulation of NMDAR subunits GluN1, GluN2A, and GluN2D on reward induced by dorsal raphe electrical stimulation. Reward thresholds were measured before and 24 h after each of three consecutive daily bilateral microinjections of siRNA for the targeted receptor subunit(s) or non-active RNA sequence. After the last measurement, reward thresholds were reassessed following a bilateral microinjection of the preferred GluN2A-NMDA antagonist, (2R,4S)-4-(3-Phosphopropyl)-2-piperidinecarboxylic acid (PPPA). Western-blot analysis showed that siRNAs reduced GluN1-and GluN2A-containing receptors whereas behavioral tests showed that only a reduction in GluN1 produced reward attenuation. Despite NMDAR reduction, reward-enhancing effect of PPPA remained unchanged. We conclude that VM glutamate relays the reward signal initiated by dorsal raphe electrical stimulation by acting on NMDARs devoid of GluN2A/2D subunits and exerts an inhibition on this reward signal by acting on GluN2A-containing NMDARs most likely located on afferent terminals.

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Section: Discussionmentioning

confidence: 99%

Reduction in Ventral Midbrain NMDA Receptors Reveals Two Opposite Modulatory Roles for Glutamate on Reward

Hernández

Khodami-Pour

Lévesque

et al. 2015

Neuropsychopharmacol

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“…1) [Citri and Malenka, 2008]. These activity dependent changes occur in all excitatory synapses that use glutamate as their neurotransmitter as well as in some inhibitory GABAergic synapses [Nugent and Kauer, 2008]. They can be mediated by changes in the release of neurotransmitter from presynaptic terminals as well as changes in the number of excitatory receptors on postsynaptic neurons.…”

Section: Activity-dependent Neuronal Plasticitymentioning

confidence: 99%

Plasticity in the developing brain: Implications for rehabilitation

Johnston

2009

Dev Disabil Res Revs

435

273

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Neuronal plasticity allows the central nervous system to learn skills and remember information, to reorganize neuronal networks in response to environmental stimulation, and to recover from brain and spinal cord injuries. Neuronal plasticity is enhanced in the developing brain and it is usually adaptive and beneficial but can also be maladaptive and responsible for neurological disorders in some situations. Basic mechanisms that are involved in plasticity include neurogenesis, programmed cell death, and activity-dependent synaptic plasticity. Repetitive stimulation of synapses can cause long-term potentiation or long-term depression of neurotransmission. These changes are associated with physical changes in dendritic spines and neuronal circuits. Overproduction of synapses during postnatal development in children contributes to enhanced plasticity by providing an excess of synapses that are pruned during early adolescence. Clinical examples of adaptive neuronal plasticity include reorganization of cortical maps of the fingers in response to practice playing a stringed instrument and constraint-induced movement therapy to improve hemiparesis caused by stroke or cerebral palsy. These forms of plasticity are associated with structural and functional changes in the brain that can be detected with magnetic resonance imaging, positron emission tomography, or transcranial magnetic stimulation (TMS). TMS and other forms of brain stimulation are also being used experimentally to enhance brain plasticity and recovery of function. Plasticity is also influenced by genetic factors such as mutations in brain-derived neuronal growth factor. Understanding brain plasticity provides a basis for developing better therapies to improve outcome from acquired brain injuries. ' 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 200915:94-101.

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“…Indeed, excitatory synapses onto interneurons have been shown to undergo LTP and LTD (Kullmann and Lamsa, 2007). Moreover, inhibitory synapses from interneurons onto pyramidal cells also display LTP and LTD (Nugent and Kauer, 2008). Such bidirectional modifications in excitation or inhibition have been implicated in the regulation of temporal fidelity of firing and synchronization of extensive hippocampal circuits (Traub et al, 2004;Kullmann and Lamsa, 2007;Pelletier and Lacaille, 2008).…”

Section: Introductionmentioning

confidence: 99%

Persistent Transcription- and Translation-Dependent Long-Term Potentiation Induced by mGluR1 in Hippocampal Interneurons

Ran¹,

Laplante²,

Bourgeois³

et al. 2009

J. Neurosci.

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Hippocampal interneurons synchronize the activity of large neuronal ensembles during memory consolidation. Although the latter process is manifested as increases in synaptic efficacy which require new protein synthesis in pyramidal neurons, it is unknown whether such enduring plasticity occurs in interneurons. Here, we uncover a long-term potentiation (LTP) of transmission at individual interneuron excitatory synapses which persists for at least 24 h, after repetitive activation of type-1 metabotropic glutamate receptors [mGluR1-mediated chemical late LTP (cL-LTP mGluR1 )]. cL-LTP mGluR1 involves presynaptic and postsynaptic expression mechanisms and requires both transcription and translation via phosphoinositide 3-kinase/mammalian target of rapamycin and MAP kinase kinaseextracellular signal-regulated protein kinase signaling pathways. Moreover, cL-LTP mGluR1 involves translational control at the level of initiation as it is prevented by hippuristanol, an inhibitor of eIF4A, and facilitated in mice lacking the cap-dependent translational repressor, 4E-BP. Our results reveal novel mechanisms of long-term synaptic plasticity that are transcription and translation-dependent in inhibitory interneurons, indicating that persistent synaptic modifications in interneuron circuits may contribute to hippocampaldependent cognitive processes.

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LTP of GABAergic synapses in the ventral tegmental area and beyond

Cited by 72 publications

References 64 publications

Reduction in Ventral Midbrain NMDA Receptors Reveals Two Opposite Modulatory Roles for Glutamate on Reward

Reduction in Ventral Midbrain NMDA Receptors Reveals Two Opposite Modulatory Roles for Glutamate on Reward

Plasticity in the developing brain: Implications for rehabilitation

Persistent Transcription- and Translation-Dependent Long-Term Potentiation Induced by mGluR1 in Hippocampal Interneurons

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