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.

Suppression of the glutamate receptor delta 2 subunit produces a specific impairment in cerebellar long-term depression

1996 ◽  
Vol 76 (5) ◽  
pp. 3578-3583 ◽  
Author(s):  
A. Jeromin ◽  
R. L. Huganir ◽  
D. J. Linden
Keyword(s):  
Glutamate Receptor ◽  
Antisense Oligonucleotide ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Calcium Influx ◽  
Long Term Depression ◽  
Metabotropic Glutamate ◽  
Flow Through

1. The role of the glutamate receptor subunit delta 2 in the induction of cerebellar long-term depression (LTD) was investigated by application of antisense oligonucleotides. The delta 2 subunit is selectively localized to Purkinje cells (PCs), with the highest levels being in the PC dendritic spines, where parallel fibers are received and where cerebellar LTD is expressed. 2. Immunocytochemical analysis of calbindin-positive PCs revealed that both the dendritic and somatic expression of delta 2 was reduced in antisense-but not in sense-treated cultures. An antisense oligonucleotide directed against the related subunit delta 1 did not affect the expression of delta 2 in PCs. 3. Cerebellar LTD may be reliably induced in a preparation of cultured embryonic cerebellar neurons from the mouse when parallel and climbing fiber stimulation are replaced by brief glutamate pulses and strong, direct depolarization of the PC, respectively. Application of an antisense oligonucleotide directed against delta 2 completely blocked the induction of LTD produced by glutamate/ depolarization conjunctive stimulation. A delta 2 sense oligonucleotide or an antisense oligonucleotide directed against the related delta 1 subunit had no effect. 4. The effect of the delta 2 antisense oligonucleotide was not related to attenuation of calcium influx via voltage-gated channels or calcium mobilization via metabotropic glutamate receptors, as assessed with fura-2 microfluorimetry. Current flow through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-associated ion channels also appeared unaltered. All three of these processes have previously been shown to be required for cerebellar LTD induction. The observation that delta 2 is involved in a metabotropic-glutamate-receptor-independent signaling pathway that is required for LTD induction supports the view that delta 2 participates in the formation of a novel postsynaptic receptor complex.

Group 2 metabotropic glutamate receptors induced long term depression in mouse striatal slices

2001 ◽  
Vol 316 (3) ◽  
pp. 178-182 ◽  
Author(s):  
Laetitia Kahn ◽  
Gérard Alonso ◽  
David Robbe ◽  
Joël Bockaert ◽  
Olivier J. Manzoni
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Long Term Depression ◽  
Striatal Slices ◽  
Metabotropic Glutamate ◽  
Group 2

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.

scholarly journals A characterisation of long‐term depression induced by metabotropic glutamate receptor activation in the rat hippocampus in vitro

2001 ◽  
Vol 537 (2) ◽  
pp. 421-430 ◽  
Author(s):  
Stephen M. Fitzjohn ◽  
Mary J. Palmer ◽  
Jolyon E. R. May ◽  
Anne Neeson ◽  
Stephen A. C. Morris ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Activation ◽  
Rat Hippocampus ◽  
Long Term Depression ◽  
Metabotropic Glutamate

Metabotropic Glutamate Receptor-mediated LTD Involves two Interacting Ca2+ Sensors, NCS-1 and PICK1

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
J. Jo ◽  
S. Heon ◽  
M.J. Kim ◽  
G.H. Son ◽  
Y. Park ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Perirhinal Cortex ◽  
Dependent Manner ◽  
Specific Requirement ◽  
Long Term Depression ◽  
Bar Domain ◽  
Metabotropic Glutamate ◽  
The Central Nervous System

There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system, which require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex we have directly compared the Ca2+ signalling mechanisms involved in NMDAR-LTD and mGluR-LTD. Whilst both forms of LTD involve Ca2+ release from intracellular stores the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, whilst mGluR-LTD involves the neuronal Ca2+ sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC as well as protein interacting with C-kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1, via its BAR domain, in a Ca2+-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 is a component of a novel mechanism involved in mGluR-LTD.

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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