scholarly journals On the effect of ATP in long-term depression of the prefrontal cortex

2018 ◽  
Author(s):  
Jose Guzman
Keyword(s):  
Prefrontal Cortex ◽  
Metabotropic Glutamate Receptors ◽  
Pyramidal Cells ◽  
P2y Receptors ◽  
Brain Regions ◽  
Long Term Depression ◽  
Group I ◽  
Short Period

Long-term depression (LTD) of the excitatory synaptic responses constitute a cellular model of some types of memory. We found that LTD can be induced in pyramidal cells of the layer 5 in the prefrontal cortex (PFC) under certain specific associative conditions. Low-frequency stimulation at 1Hz paired with a modest postsynaptic depolarization produced LTD of excitatory postsynaptic currents (EPSCs). LTD required the release of glutamate which acted on the postsynaptic group I metabotropic glutamate receptors (mGluRs). However, the unique action of the glutamate neurotransmission was not enough to induce LTD. A simultaneous postsynaptic depolarization to activate the voltage-sensitive Ca2+ channels (VSCCs) was required to produce prefrontal LTD. Accordingly, pharmacological or electricalblockade of VSCCs prevented LTD. The co-activation of both mGluRs producing inositol-1,4,5-trisphosphate (InsP3) and VSCCs which provide a rise in Ca2+ at thepostsynaptic dendritic sites converge on the intracellular InsP3 receptors. Thesereceptors release Ca2+ from intracellular stores, which in turn activate the phosphatases calcineurin and PP1 to induce prefrontal LTD.ATP has been shown to exert a variety of modulatory effects in various brain regions through ionotropic (P2X) and metabotropic (P2Y) receptors. As far as the medial prefrontal cortex transmission is concerned, ATP exerts its effect acting preferentially via P2Y receptors, which are located in neuronal and glial cell populations.Activation of P2Y1,12,13 receptors with ADP-beta-S prevented LTD, and this effect wasabolished with the co-application of a specific P2Y1 receptor antagonist. Moreover,the ADP-beta-S blockade of prefrontal LTD was absent in P2Y1 knock-out mice, but not in P2Y2 knock-outs, supporting the role of P2Y1 receptors in the modulation of LTD.ATP released endogenously may affect LTD. The release of ATP can be favored with trains of stimulations at high frequencies (i.e., 100Hz or tetanus). Tetanic stimulation apparently released ATP in the PFC, because cells which did not show LTD during tetanus became plastic under application of P2Y antagonists and presented LTD. Additionally, large amounts of ATP released during an in vitro model of hypoxia were also able to prevent LTD. Similarly, application of a P2Y antagonist during hypoxia in vitro recovered LTD. These two mechanisms represent a way by which endogenous ATP may impair the development of LTD in the PFC through the activation of P2Y receptors and may explain the short period of amnesia characteristic of the cortical oxygen deprivation produced during hypoxia.

scholarly journals Homer 1a Suppresses Neocortex Long-Term Depression in a Cortical Layer-Specific Manner

2008 ◽  
Vol 99 (2) ◽  
pp. 950-957 ◽  
Author(s):  
Yoshifumi Ueta ◽  
Ryo Yamamoto ◽  
Shigeki Sugiura ◽  
Kaoru Inokuchi ◽  
Nobuo Kato
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Pyramidal Cells ◽  
Cortical Layer ◽  
Long Term Depression ◽  
Group I ◽  
Specific Manner ◽  
Group I Mglurs ◽  
Layer V ◽  
Layer Vi

Homer1a/Vesl-1S is an activity-dependently induced member of the scaffold protein family Homer/Vesl, which is known to link group I metabotropic glutamate receptors (mGluRs) to endoplasmic calcium release channels and to regulate them. Here we studied roles of Homer 1a in inducing long-term depression (LTD) in rat visual cortex slices. Homer 1a protein was injected by diffusion from whole cell patch pipettes. In layer VI pyramidal cells, LTD was reduced in magnitude with Homer 1a. LTD in layer VI was suppressed by applying antagonists of mGluR5, a subtype of group I mGluRs expressed with higher density than mGluR1 in neocortex pyramidal cells, or inositol-1,4,5-triphosphate receptors (IP3Rs) but not that against N-methyl-d-aspartate receptors (NMDARs). In layer II/III or layer V, Homer 1a injection was unable to affect LTD, which is mostly dependent on NMDARs and not on group I mGluRs in these layers. To examine the effects of endogenous Homer 1a, electroconvulsive shock (ECS) was applied. Homer 1a thereby induced, as did Homer 1a injection, reduced LTD magnitude in layer VI pyramidal cells and failed to do so in layer II/III or layer V pyramidal cells. These results indicate that both exo- and endogenous Homer 1a suppressed LTD in a cortical layer-specific manner, and its layer-specificity may be explained by the high affinity of Homer 1a to group I mGluRs.

Activation of Group I mGluRs Is Necessary for Induction of Long-Term Depression at Striatal Synapses

2001 ◽  
Vol 86 (5) ◽  
pp. 2405-2412 ◽  
Author(s):  
Ki-Wug Sung ◽  
Sukwoo Choi ◽  
David M. Lovinger
Keyword(s):  
Synaptic Transmission ◽  
Metabotropic Glutamate Receptors ◽  
Brain Slices ◽  
High Frequency Stimulation ◽  
Long Term Depression ◽  
Selective Antagonist ◽  
Group I ◽  
Group Ii ◽  
Mglur Antagonist

Activation of metabotropic glutamate receptors (mGluRs), which are coupled to G proteins, has important roles in certain forms of synaptic plasticity including corticostriatal long-term depression (LTD). In the present study, extracellular field potential and whole cell voltage-clamp recording techniques were used to investigate the effect of mGluR antagonists with different subtype specificity on high-frequency stimulation (HFS)-induced LTD of synaptic transmission in the striatum of brain slices obtained from 15-to 25-day-old rats. Induction of LTD was prevented during exposure to the nonselective mGluR antagonist (RS)-α-methyl-4-carboxyphenylglycine (500 μM). The group I mGluR-selective antagonists ( S)-4-carboxy-phenylglycine (50 μM) and (RS)-1-aminoindan-1,5-dicarboxylic acid (100 μM) prevented induction of LTD when applied before and during HFS. The mGluR1-selective antagonist 7-(Hydroxyimino) cyclopropa[b]chromen-1a-carboxylate ethyl ester (80 μM) also blocked LTD induction. Unexpectedly, the mGluR5-selective antagonist 2-methyl-6-(phenylethyl)-pyridine (10 μM) also prevented LTD induction. The group II mGluR antagonist LY307452 (10 μM) did not block LTD induction at corticostriatal synapses, but LY307452 was able to block transient synaptic depression induced by the group II agonist LY314593. None of the antagonists had any effect on basal synaptic transmission at the concentrations used, and mGluR antagonists did not reverse LTD when applied beginning 20 min after HFS. These results suggest that both group I mGluR subtypes contribute to the induction of LTD at corticostriatal synapses.

scholarly journals Long-Term Depression of Striatal DA Release Induced by mGluRs via Sustained Hyperactivity of Local Cholinergic Interneurons

2021 ◽  
Vol 15 ◽  
Author(s):  
Nicola B. Mercuri ◽  
Mauro Federici ◽  
Francesca Romana Rizzo ◽  
Lorenzo Maugeri ◽  
Sebastian L. D’Addario ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Depression ◽  
Striatal Slices ◽  
Metabotropic Glutamate ◽  
Cholinergic Interneurons ◽  
Da Release

The cellular mechanisms regulating dopamine (DA) release in the striatum have attracted much interest in recent years. By in vitro amperometric recordings in mouse striatal slices, we show that a brief (5 min) exposure to the metabotropic glutamate receptor agonist DHPG (50 μM) induces a profound depression of synaptic DA release, lasting over 1 h from DHPG washout. This long-term depression is sensitive to glycine, which preferentially inhibits local cholinergic interneurons, as well as to drugs acting on nicotinic acetylcholine receptors and to the pharmacological depletion of released acetylcholine. The same DHPG treatment induces a parallel long-lasting enhancement in the tonic firing of presumed striatal cholinergic interneurons, measured with multi-electrode array recordings. When DHPG is bilaterally infused in vivo in the mouse striatum, treated mice display an anxiety-like behavior. Our results demonstrate that metabotropic glutamate receptors stimulation gives rise to a prolonged depression of the striatal dopaminergic transmission, through a sustained enhancement of released acetylcholine, due to the parallel long-lasting potentiation of striatal cholinergic interneurons firing. This plastic interplay between dopamine, acetylcholine, and glutamate in the dorsal striatum may be involved in anxiety-like behavior typical of several neuropsychiatric disorders.

scholarly journals Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction

2015 ◽  
Vol 112 (4) ◽  
pp. 1196-1201 ◽  
Author(s):  
Adam G. Walker ◽  
Cody J. Wenthur ◽  
Zixiu Xiang ◽  
Jerri M. Rook ◽  
Kyle A. Emmitte ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Fear Extinction ◽  
Long Term Depression ◽  
Metabotropic Glutamate ◽  
Metabotropic Glutamate Receptor 3

Clinical studies have revealed that genetic variations in metabotropic glutamate receptor 3 (mGlu3) affect performance on cognitive tasks dependent upon the prefrontal cortex (PFC) and may be linked to psychiatric conditions such as schizophrenia, bipolar disorder, and addiction. We have performed a series of studies aimed at understanding how mGlu3 influences PFC function and cognitive behaviors. In the present study, we found that activation of mGlu3 can induce long-term depression in the mouse medial PFC (mPFC) in vitro. Furthermore, in vivo administration of a selective mGlu3 negative allosteric modulator impaired learning in the mPFC-dependent fear extinction task. The results of these studies implicate mGlu3 as a major regulator of PFC function and cognition. Additionally, potentiators of mGlu3 may be useful in alleviating prefrontal impairments associated with several CNS disorders.

Induction of NMDA Receptor-Dependent Long-Term Depression in Visual Cortex Does Not Require Metabotropic Glutamate Receptors

1999 ◽  
Vol 82 (6) ◽  
pp. 3594-3597 ◽  
Author(s):  
Nathaniel B. Sawtell ◽  
Kimberly M. Huber ◽  
John C. Roder ◽  
Mark F. Bear
Keyword(s):  
Visual Cortex ◽  
Nmda Receptor ◽  
Metabotropic Glutamate Receptors ◽  
Low Frequency ◽  
Long Term Depression ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Frequency Stimulation ◽  
Visual Cortical

We tested the role of group I mGluRs in the induction of long-term depression (LTD) in the visual cortex, using the novel mGluR antagonist LY341495 and mice lacking mGluR5, the predominant phosphoinositide (PI)-linked mGluR in the visual cortex. We find that LY341495 is a potent blocker of glutamate-stimulated PI hydrolysis in visual cortical synaptoneurosomes, and that it effectively antagonizes the actions of the mGluR agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (ACPD) on synaptic transmission in visual cortical slices. However, LY341495 has no effect on the induction of LTD by low-frequency stimulation. Furthermore, mice lacking mGluR5 show normal NMDA receptor-dependent LTD. These results indicate that group I mGluR activation is not required for the induction of NMDA receptor-dependent LTD in the visual cortex.

scholarly journals mGluR1, but not mGluR5, activates feed-forward inhibition in the medial prefrontal cortex to impair decision making

2011 ◽  
Vol 106 (2) ◽  
pp. 960-973 ◽  
Author(s):  
Hao Sun ◽  
Volker Neugebauer
Keyword(s):  
Decision Making ◽  
Prefrontal Cortex ◽  
Metabotropic Glutamate Receptors ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Synaptic Inhibition ◽  
Feed Forward ◽  
Postsynaptic Currents ◽  
Group I ◽  
Feed Forward Inhibition

Cognitive flexibility depends on the integrity of the prefrontal cortex (PFC). We showed previously that impaired decision making in pain results from amygdala-driven inhibition of medial PFC neurons, but the underlying mechanisms remain to be determined. Using whole cell patch clamp in rat brain slices and a cognitive behavioral task, we tested the hypothesis that group I metabotropic glutamate receptors (mGluRs) activate feed-forward inhibition to decrease excitability and output function of PFC pyramidal cells, thus impairing decision making. Polysynaptic inhibitory postsynaptic currents (IPSCs) and monosynaptic excitatory postsynaptic currents (EPSCs) were evoked in layer V pyramidal cells by stimulating presumed amygdala afferents. An mGluR1/5 agonist [(S)-3,5-dihydroxyphenylglycine, DHPG] increased synaptic inhibition more strongly than excitatory transmission. The facilitatory effects were blocked by an mGluR1 [( S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid, LY367385], but not mGluR5, antagonist, 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine. IPSCs were blocked by bicuculline and decreased by 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt (NBQX). Facilitation of synaptic inhibition by DHPG was glutamate driven because it was blocked by NBQX. DHPG increased frequency but not amplitude of spontaneous IPSCs; consistent with action potential-dependent synaptic inhibition, tetrodotoxin (TTX) prevented the facilitatory effects. DHPG decreased synaptically evoked spikes (E-S coupling) and depolarization-induced spiking [frequency-current ( f-I) relationship]. This effect was indirect, resulting from glutamate-driven synaptic inhibition, because it persisted when a G protein blocker was included in the pipette but was blocked by GABAA receptor antagonists and NBQX. In contrast, DHPG increased E-S coupling and f-I relationships in mPFC interneurons through a presynaptic action, further supporting the concept of feed-forward inhibition. DHPG also impaired the ability of the animals to switch strategies in a decision-making task; bicuculline restored normal decision making, whereas a GABAA receptor agonist (muscimol) mimicked the decision-making deficit. The results show that mGluR1 activates feed-forward inhibition of PFC pyramidal cells to impair cognitive functions.

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