Specialized Inhibitory Synaptic Actions Between Nearby Neocortical Pyramidal Neurons

Ren, Ming; Yoshimura, Yumiko; Takada, Naoki; Horibe, Shoko; Komatsu, Yukio

doi:10.1126/science.1135468

Cited by 70 publications

(70 citation statements)

References 30 publications

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“…Facilitation of GABA release has been observed in basolateral amygdala neurons following GluR5 receptor activation with low concentrations of ATPA (Braga et al, 2003). Although presynaptic KARs located on terminals of fast-spiking GABAergic interneurons have been reported to decrease inhibitory transmitter release onto layer V neocortical pyramidal cells (Ali et al, 2001), our present results, and those of others (Ren et al, 2007) indicate that evoked and spontaneous IPSCs in superficial layers of neocortex are potently facilitated by activation of presynaptic KARs.…”

Section: Presynaptic Ka Receptors Mediate Ipsc Facilitationsupporting

confidence: 51%

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Calcium release via activation of presynaptic IP3 receptors contributes to kainate-induced IPSC facilitation in rat neocortex

Mathew

Hablitz

2008

Neuropharmacology

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We examined the mechanisms of kainate (KA) induced modulation of GABA release in rat prefrontal cortex. Pharmacologically isolated IPSCs were recorded from visually identified layer II/III pyramidal cells using whole cell patch clamp techniques. KA produced an increase in evoked IPSC amplitude at low nanomolar concentrations (100-500 nM). The frequency but not the amplitude of miniature (m) IPSCs was also increased. The GluR5 subunit selective agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) caused an increase in mIPSC frequency whereas (3S,4aR,6S,8aR)-6-(4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid (LY382884), a selective GluR5 subunit antagonist, inhibited this facilitation. Philanthotoxin-433 (PhTx) blocked the effect of KA, indicating involvement of Ca 2+ -permeable GluR5 receptors. No IPSC facilitation was seen when Ca 2+ was omitted from the bathing solution. Facilitation was observed when slices were preincubated in ruthenium red or high concentrations of ryanodine, but was inhibited with application of thapsigargin. The IP3 receptor (IP3R) antagonists diphenylboric acid 2-amino-ethyl ester (2-APB) (15 µM) and Xestospongin C (XeC) blocked IPSC facilitation. These results show that activation of KA receptors (KARs) on GABAergic nerve terminals results is linked to intracellular Ca 2+ release via activation of IP3, but not ryanodine, receptors. This represents a new mechanism of presynaptic modulation whereby Ca 2+ entry thru Ca 2+ -permeable GluR5 subunit containing KARs activates IP3Rs receptors leading to an increase in GABA release.

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Section: Presynaptic Ka Receptors Mediate Ipsc Facilitationsupporting

confidence: 51%

“…KARs could depolarize GABAergic terminals and facilitate IPSCs via activation of voltagedependent Ca 2+ channels (Ren et al, 2007). To test this, 200 µM Cd 2+ was applied.…”

Section: Role Of Extracellular Ca 2+ In Kainate Mipsc Facilitationmentioning

confidence: 99%

Calcium release via activation of presynaptic IP3 receptors contributes to kainate-induced IPSC facilitation in rat neocortex

Mathew

Hablitz

2008

Neuropharmacology

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“…There is evidence that presynaptic NMDARs are localized in GABAergic terminals of several brain areas including the VM (Paquet and Smith, 2000) and their role seems to modulate the strength of synaptic transmission by varying the likelihood of neurotransmitter release (Pinheiro and Mulle, 2008). In most brain areas, the presence of presynaptic NMDARs contribute to release of inhibitory neurotransmitter in the cerebral cortex (Mathew and Hablitz, 2011;Ren et al, 2007), lateral amygdala (Humeau et al, 2003), cerebellum (Bidoret et al, 2009), entorhinal cortex (Chamberlain et al, 2008), and visual cortex (Li et al, 2008). In general these studies demonstrate that inhibition can be potentiated by axoaxonic contacts without the need for somatic interneuron firing; such mechanism alters the weight between excitatory and inhibitory inputs and therefore alters the output of the neuronal circuit.…”

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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“…Postsynaptic recordings of miniature IPSCs also indicate that kainate activates presynaptic receptors on GABAergic nerve terminals in hippocampus (Rodriguez-Moreno et al, 1997;Frerking et al, 1999;Mulle et al, 2000;Cossart et al, 2001) and neocortex (Ali et al, 2001;Ren et al, 2007). Recent advances in imaging technology have made it possible to directly monitor spontaneous and activity-dependent synaptic vesicle recycling in brain slices using the styryl dye FM1-43 (Stanton et al, 2001;Zakharenko et al, 2001;Brager et al, 2003;Axmacher et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Kainate Modulates Presynaptic GABA Release from Two Vesicle Pools

Mathew¹,

Pozzo-Miller²,

Hablitz³

2008

J. Neurosci.

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Inhibitory control of local neuronal circuits is critical for prefrontal cortical functioning. Modulation of inhibitory circuits by several neuromodulators has been demonstrated, but the underlying mechanisms are unclear. Neuromodulator effects on synaptic vesicle recycling have received little attention. Controversy also exists whether different pools of synaptic vesicles underlie spontaneous and activity-dependent vesicle recycling. We therefore investigated the effects of kainate receptor activation on GABA release in rat prefrontal neocortex using electrophysiological and styryl dye imaging techniques in acute neocortical slices. Electrophysiological studies demonstrated that activation of kainate receptors increased the frequency, but not the amplitude of miniature IPSCs, suggesting a presynaptic action. Using styryl dye staining and multiphoton excitation microscopy, we visualized vesicular release from inhibitory GABAergic terminals in prefrontal cortical slices and demonstrate that kainate facilitates GABA release from presynaptic terminals. Our findings also indicate the presence of two pools of GABA-containing vesicles within inhibitory terminals. Kainate modulates both pools but only when vesicles are endocytosed and exocytosed by matching protocols of dye loading, i.e., spontaneous or evoked afferent activity.

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Specialized Inhibitory Synaptic Actions Between Nearby Neocortical Pyramidal Neurons

Cited by 70 publications

References 30 publications

Calcium release via activation of presynaptic IP3 receptors contributes to kainate-induced IPSC facilitation in rat neocortex

Calcium release via activation of presynaptic IP3 receptors contributes to kainate-induced IPSC facilitation in rat neocortex

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

Kainate Modulates Presynaptic GABA Release from Two Vesicle Pools

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