Cranial afferent glutamate heterosynaptically modulates GABA release onto second-order neurons via distinctly segregated metabotropic glutamate receptors

Young Ho Jin, Timothy W. Bailey, Michael Andresen

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The balance between excitation and inhibition dictates central integration. Glutamatergic and GABAergic neurotransmission dominate this process. Cranial primary afferents enter the brainstem to release glutamate (Glu) onto second-order neurons within the caudal nucleus tractus solitarius (NTS) to initiate autonomic reflexes. The simplest pathways for these reflexes contain as few as two central neurons, but display robust frequency-dependent behavior. Within NTS, multiple metabotropic Glu receptors (mGluRs) are present, but their roles are poorly understood. Using synaptically discriminated second-order NTS neurons in brainstem slices and mechanically dissociated NTS neurons with intact boutons, we show that Glu differentially controls GABA release via distinct presynaptic mGluRs. In second-order NTS neurons recorded in slices, activation of primary afferents at frequencies as low as 10 shocks per second released sufficient Glu to alter rates of spontaneous IPSCs (sIPSCs). In both approaches, group I mGluRs increased GABA release in some neurons, but, on different neurons, group II and group III mGluRs decreased the sIPSC rate. mGluR actions were remarkably rapid, with onset and reversal beginning within 100 msec. In all cases, mGluR actions were exclusively presynaptic, and mGluRs did not alter postsynaptic properties in second-order neurons in either slices or isolated neurons. Tests with capsaicin and αβ-methylene ATP suggest that myelinated and unmyelinated afferent pathways engageboth mGluR-GABA mechanisms. Afferent Glu spillover provides heterosynaptic cross talk with GABAergic inhibition in NTS. This process may critically shape the dynamic character and use dependence for cranial afferent transmission at the first stage of autonomic reflexes.

Original languageEnglish (US)
Pages (from-to)9332-9340
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number42
DOIs
StatePublished - Oct 20 2004

Fingerprint

Metabotropic Glutamate Receptors
gamma-Aminobutyric Acid
Glutamic Acid
Solitary Nucleus
Neurons
Reflex
Brain Stem
Afferent Pathways
GABA Receptors
Capsaicin
Synaptic Transmission
Shock
Adenosine Triphosphate

Keywords

  • Afferent
  • Autonomic
  • Baroreceptor
  • Brainstem
  • GABA
  • Glutamate
  • Heterosynaptic
  • Metabotropic
  • Nucleus tractus solitarius
  • Presynaptic modulation
  • Sensory neurons
  • Slice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cranial afferent glutamate heterosynaptically modulates GABA release onto second-order neurons via distinctly segregated metabotropic glutamate receptors. / Jin, Young Ho; Bailey, Timothy W.; Andresen, Michael.

In: Journal of Neuroscience, Vol. 24, No. 42, 20.10.2004, p. 9332-9340.

Research output: Contribution to journalArticle

@article{9a63471f582344f3a9df8569c74d089e,
title = "Cranial afferent glutamate heterosynaptically modulates GABA release onto second-order neurons via distinctly segregated metabotropic glutamate receptors",
abstract = "The balance between excitation and inhibition dictates central integration. Glutamatergic and GABAergic neurotransmission dominate this process. Cranial primary afferents enter the brainstem to release glutamate (Glu) onto second-order neurons within the caudal nucleus tractus solitarius (NTS) to initiate autonomic reflexes. The simplest pathways for these reflexes contain as few as two central neurons, but display robust frequency-dependent behavior. Within NTS, multiple metabotropic Glu receptors (mGluRs) are present, but their roles are poorly understood. Using synaptically discriminated second-order NTS neurons in brainstem slices and mechanically dissociated NTS neurons with intact boutons, we show that Glu differentially controls GABA release via distinct presynaptic mGluRs. In second-order NTS neurons recorded in slices, activation of primary afferents at frequencies as low as 10 shocks per second released sufficient Glu to alter rates of spontaneous IPSCs (sIPSCs). In both approaches, group I mGluRs increased GABA release in some neurons, but, on different neurons, group II and group III mGluRs decreased the sIPSC rate. mGluR actions were remarkably rapid, with onset and reversal beginning within 100 msec. In all cases, mGluR actions were exclusively presynaptic, and mGluRs did not alter postsynaptic properties in second-order neurons in either slices or isolated neurons. Tests with capsaicin and αβ-methylene ATP suggest that myelinated and unmyelinated afferent pathways engageboth mGluR-GABA mechanisms. Afferent Glu spillover provides heterosynaptic cross talk with GABAergic inhibition in NTS. This process may critically shape the dynamic character and use dependence for cranial afferent transmission at the first stage of autonomic reflexes.",
keywords = "Afferent, Autonomic, Baroreceptor, Brainstem, GABA, Glutamate, Heterosynaptic, Metabotropic, Nucleus tractus solitarius, Presynaptic modulation, Sensory neurons, Slice",
author = "Jin, {Young Ho} and Bailey, {Timothy W.} and Michael Andresen",
year = "2004",
month = "10",
day = "20",
doi = "10.1523/JNEUROSCI.1991-04.2004",
language = "English (US)",
volume = "24",
pages = "9332--9340",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "42",

}

TY - JOUR

T1 - Cranial afferent glutamate heterosynaptically modulates GABA release onto second-order neurons via distinctly segregated metabotropic glutamate receptors

AU - Jin, Young Ho

AU - Bailey, Timothy W.

AU - Andresen, Michael

PY - 2004/10/20

Y1 - 2004/10/20

N2 - The balance between excitation and inhibition dictates central integration. Glutamatergic and GABAergic neurotransmission dominate this process. Cranial primary afferents enter the brainstem to release glutamate (Glu) onto second-order neurons within the caudal nucleus tractus solitarius (NTS) to initiate autonomic reflexes. The simplest pathways for these reflexes contain as few as two central neurons, but display robust frequency-dependent behavior. Within NTS, multiple metabotropic Glu receptors (mGluRs) are present, but their roles are poorly understood. Using synaptically discriminated second-order NTS neurons in brainstem slices and mechanically dissociated NTS neurons with intact boutons, we show that Glu differentially controls GABA release via distinct presynaptic mGluRs. In second-order NTS neurons recorded in slices, activation of primary afferents at frequencies as low as 10 shocks per second released sufficient Glu to alter rates of spontaneous IPSCs (sIPSCs). In both approaches, group I mGluRs increased GABA release in some neurons, but, on different neurons, group II and group III mGluRs decreased the sIPSC rate. mGluR actions were remarkably rapid, with onset and reversal beginning within 100 msec. In all cases, mGluR actions were exclusively presynaptic, and mGluRs did not alter postsynaptic properties in second-order neurons in either slices or isolated neurons. Tests with capsaicin and αβ-methylene ATP suggest that myelinated and unmyelinated afferent pathways engageboth mGluR-GABA mechanisms. Afferent Glu spillover provides heterosynaptic cross talk with GABAergic inhibition in NTS. This process may critically shape the dynamic character and use dependence for cranial afferent transmission at the first stage of autonomic reflexes.

AB - The balance between excitation and inhibition dictates central integration. Glutamatergic and GABAergic neurotransmission dominate this process. Cranial primary afferents enter the brainstem to release glutamate (Glu) onto second-order neurons within the caudal nucleus tractus solitarius (NTS) to initiate autonomic reflexes. The simplest pathways for these reflexes contain as few as two central neurons, but display robust frequency-dependent behavior. Within NTS, multiple metabotropic Glu receptors (mGluRs) are present, but their roles are poorly understood. Using synaptically discriminated second-order NTS neurons in brainstem slices and mechanically dissociated NTS neurons with intact boutons, we show that Glu differentially controls GABA release via distinct presynaptic mGluRs. In second-order NTS neurons recorded in slices, activation of primary afferents at frequencies as low as 10 shocks per second released sufficient Glu to alter rates of spontaneous IPSCs (sIPSCs). In both approaches, group I mGluRs increased GABA release in some neurons, but, on different neurons, group II and group III mGluRs decreased the sIPSC rate. mGluR actions were remarkably rapid, with onset and reversal beginning within 100 msec. In all cases, mGluR actions were exclusively presynaptic, and mGluRs did not alter postsynaptic properties in second-order neurons in either slices or isolated neurons. Tests with capsaicin and αβ-methylene ATP suggest that myelinated and unmyelinated afferent pathways engageboth mGluR-GABA mechanisms. Afferent Glu spillover provides heterosynaptic cross talk with GABAergic inhibition in NTS. This process may critically shape the dynamic character and use dependence for cranial afferent transmission at the first stage of autonomic reflexes.

KW - Afferent

KW - Autonomic

KW - Baroreceptor

KW - Brainstem

KW - GABA

KW - Glutamate

KW - Heterosynaptic

KW - Metabotropic

KW - Nucleus tractus solitarius

KW - Presynaptic modulation

KW - Sensory neurons

KW - Slice

UR - http://www.scopus.com/inward/record.url?scp=7044227666&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7044227666&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1991-04.2004

DO - 10.1523/JNEUROSCI.1991-04.2004

M3 - Article

C2 - 15496669

AN - SCOPUS:7044227666

VL - 24

SP - 9332

EP - 9340

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 42

ER -