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.

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.

Group I mGluRs Increase Excitability of Hippocampal CA1 Pyramidal Neurons by a PLC-Independent Mechanism

2002 ◽  
Vol 88 (1) ◽  
pp. 107-116 ◽  
Author(s):  
David R. Ireland ◽  
Wickliffe C. Abraham
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Receptor Subtypes ◽  
Ca1 Pyramidal Neurons ◽  
Group I ◽  
Hippocampal Ca1 ◽  
Group I Mglurs ◽  
Induced Changes

Previous studies have implicated phospholipase C (PLC)-linked Group I metabotropic glutamate receptors (mGluRs) in regulating the excitability of hippocampal CA1 pyramidal neurons. We used intracellular recordings from rat hippocampal slices and specific antagonists to examine in more detail the mGluR receptor subtypes and signal transduction mechanisms underlying this effect. Application of the Group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) suppressed slow- and medium-duration afterhyperpolarizations (s- and mAHP) and caused a consequent increase in cell excitability as well as a depolarization of the membrane and an increase in input resistance. Interestingly, with the exception of the suppression of the mAHP, these effects were persistent, and in the case of the sAHP lasting for more than 1 h of drug washout. Preincubation with the specific mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), reduced but did not completely prevent the effects of DHPG. However, preincubation with both MPEP and the mGluR1 antagonist LY367385 completely prevented the DHPG-induced changes. These results demonstrate that the DHPG-induced changes are mediated partly by mGluR5 and partly by mGluR1. Because Group I mGluRs are linked to PLC via G-protein activation, we also investigated pathways downstream of PLC activation, using chelerythrine and cyclopiazonic acid to block protein kinase C (PKC) and inositol 1,4,5-trisphosphate-(IP3)-activated Ca2+ stores, respectively. Neither inhibitor affected the DHPG-induced suppression of the sAHP or the increase in excitability nor did an inhibitor of PLC itself, U-73122. Taken together, these results argue that in CA1 pyramidal cells in the adult rat, DHPG activates mGluRs of both the mGluR5 and mGluR1 subtypes, causing a long-lasting suppression of the sAHP and a consequent persistent increase in excitability via a PLC-, PKC-, and IP3-independent transduction pathway.

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.

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.

Layer Variations of Long-Term Depression in Rat Visual Cortex

2004 ◽  
Vol 92 (5) ◽  
pp. 2652-2658 ◽  
Author(s):  
Yan Rao ◽  
Nigel W. Daw
Keyword(s):  
Visual Cortex ◽  
Nmda Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Depression ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Developing Rat ◽  
Layer Vi

In vitro long-term depression (LTD) is thought to be a model for the loss of cortical responsiveness to an eye deprived of vision during the critical period. Using whole cell recording, the present study investigates the mechanisms of LTD in vitro across layers in developing rat visual cortex. LTD was induced in layers II/III, V, and VI but not layer IV with 10-min 1-Hz stimulation paired with postsynaptic depolarization. LTD in layers II/III and V could be blocked by the N-methyl-d-aspartate (NMDA) receptor antagonist d-aminophosphonovaleric acid (d-AP5) but not by 100 μM (2S)-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), a metabotropic glutamate receptor inhibitor. In contrast, LTD in layer VI was blocked by 100 μM LY341495 and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) but not d-AP5 and partially blocked by application of guanosine 5′- O-(2-thiodiphosphate) thilothium salt (GDP-β-S) in patch pipette, suggesting an involvement of postsynaptic group I metabotropic glutamate receptors (mGluRs). These results indicate that LTD in developing rat visual cortex varies with layer: LTD was absent in layer IV, suggesting a unique plasticity mechanism at geniculocortical synapses; LTD in layers II/III and V depends on NMDA receptors but not mGluRs, and LTD in layer VI requires mGluRs but not NMDA receptors.

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