Metabotropic Glutamate Receptor Activation Modulates Sound Level Processing in the Cochlear Nucleus

1998 ◽  
Vol 80 (1) ◽  
pp. 209-217 ◽  
Author(s):  
Dan H. Sanes ◽  
JoAnn McGee ◽  
Edward J. Walsh
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Cochlear Nucleus ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Sound Level ◽  
Metabotropic Glutamate

Sanes, Dan H., JoAnn McGee, and Edward J. Walsh. Metabotropic glutamate receptor activation modulates sound level processing in the cochlear nucleus. J. Neurophysiol. 80: 209–217, 1998. The principal role of ionotropic glutamate receptors in the transmission and processing of information in the auditory pathway has been investigated extensively. In contrast, little is known about the functional contribution of the G-protein–coupled metabotropic glutamate receptors (mGluRs), although their anatomic location suggests that they exercise a significant influence on auditory processing. To investigate this issue, sound-evoked responses were obtained from single auditory neurons in the cochlear nuclear complex of anesthetized cats and gerbils, and metabotropic ligands were administered locally through microionophoretic pipettes. In general, microionophoresis of the mGluR agonists, (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2 S,1′ S,2′ S)-2-(carboxycyclopropyl)glycine, initially produced a gradual increase in spontaneous and sound-evoked discharge rates. However, activation and recovery times were significantly longer than those observed for ionotropic agonists, such as N-methyl-d-aspartate or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, consistent with the recruitment of a second-messenger system. The efficacy of mGluR agonists was diminished after administration of the mGluR antagonist, (+)-α-methyl-4-carboxyphenylglycine, consistent with a selective action at metabotropic recognition sites. In contrast, two distinct changes were observed after the mGluR agonist had been discontinued for several minutes. Approximately 50% of neurons exhibited a chronic depression of sound-evoked discharge rate reminiscent of long-term depression, a cellular property observed in other systems. Approximately 30% of neurons exhibited a long-lasting enhancement of the sound-evoked response similar to the cellular phenomenon of long-term potentiation. These findings suggest that mGluR activation has a profound influence on the gain of primary afferent driven activity in the caudal cochlear nucleus.

Intracellular Ca2+ release mediated by metabotropic glutamate receptor activation in the leech giant glial cell.

1997 ◽  
Vol 200 (19) ◽  
pp. 2565-2573
Author(s):  
C Lohr ◽  
J W Deitmer
Keyword(s):  
Membrane Potential ◽  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Glial Cells ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Cyclopiazonic Acid ◽  
Receptor Activation ◽  
Atpase Inhibitor ◽  
Metabotropic Glutamate

We have investigated the effects of glutamate and glutamate receptor ligands on the intracellular free Ca2+ concentration ([Ca2+]i) and the membrane potential (Em) of single, identified neuropile glial cells in the central nervous system of the leech Hirudo medicinalis. Exposed glial cells of isolated ganglia were filled iontophoretically with the Ca2+ indicator dye Fura-2. Application of glutamate (200-500 mumoll-1) caused biphasic membrane potential shifts and increases in [Ca2+]i, which were only partly reduced by either removing extracellular Ca2+ or blocking ionotropic glutamate receptors with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 50-100 mumol l-1. Metabotropic glutamate receptor (mGluR) ligands had the following rank of potency in inducing a rise in [Ca2+]i: quisqualate (QQ, 200 mumol l-1) > glutamate (200 mumol l-1) > L(+)2-amino-3-phosphonopropionic acid (L-AP3, 200 mumol l-1 > trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 400 mumol l-1). The mGluR-selective antagonist (RS)-alpha-methyl-4-carboxyphenylglycine [(RS)-MCPG, 1 mmol l-1] significantly reduced glutamate-evoked increases in [Ca2+]i by 20%. Incubation of the ganglia with the endoplasmic ATPase inhibitor cyclopiazonic acid (CPA, 10 mumol l-1) caused a significant (53%) reduction of glutamate-induced [Ca2+]i transients, while incubation with lithium ions (2 mmol l-1) resulted in a 46% reduction. The effects of depleting the Ca2+ stores with CPA and of CNQX were additive. We conclude that glutamate-induced [Ca2+]i transients were mediated by activation of both Ca(2+)-permeable ionotropic non-NMDA receptors and of metabotropic glutamate receptors leading to Ca2+ release from intracellular Ca2+ stores.

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.

Sign in / Sign up

Export Citation Format

Share Document