Metabotropic glutamate receptor activation modulates sound level processing in the cochlear nucleus

Dan Sanes, JoAnn Mcgee, Edward J. Walsh

Research output: Contribution to journalArticle

Abstract

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, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2S, 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 longlasting 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.

Original languageEnglish (US)
Pages (from-to)209-217
Number of pages9
JournalJournal of Neurophysiology
Volume80
Issue number1
StatePublished - Jul 1998

Fingerprint

Cochlear Nucleus
Metabotropic Glutamate Receptors
Neurons
Auditory Pathways
Ionotropic Glutamate Receptors
Gerbillinae
Long-Term Potentiation
Cochlea
Second Messenger Systems
N-Methylaspartate
Automatic Data Processing
GTP-Binding Proteins
Cats
Ligands
Acids

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Metabotropic glutamate receptor activation modulates sound level processing in the cochlear nucleus. / Sanes, Dan; Mcgee, JoAnn; Walsh, Edward J.

In: Journal of Neurophysiology, Vol. 80, No. 1, 07.1998, p. 209-217.

Research output: Contribution to journalArticle

@article{dc13a330a766486e85549fc604461c26,
title = "Metabotropic glutamate receptor activation modulates sound level processing in the cochlear nucleus",
abstract = "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, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2S, 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 longlasting 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.",
author = "Dan Sanes and JoAnn Mcgee and Walsh, {Edward J.}",
year = "1998",
month = "7",
language = "English (US)",
volume = "80",
pages = "209--217",
journal = "Journal of Neurophysiology",
issn = "0022-3077",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Metabotropic glutamate receptor activation modulates sound level processing in the cochlear nucleus

AU - Sanes, Dan

AU - Mcgee, JoAnn

AU - Walsh, Edward J.

PY - 1998/7

Y1 - 1998/7

N2 - 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, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2S, 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 longlasting 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.

AB - 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, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2S, 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 longlasting 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.

UR - http://www.scopus.com/inward/record.url?scp=0031869645&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031869645&partnerID=8YFLogxK

M3 - Article

C2 - 9658042

AN - SCOPUS:0031869645

VL - 80

SP - 209

EP - 217

JO - Journal of Neurophysiology

JF - Journal of Neurophysiology

SN - 0022-3077

IS - 1

ER -