Elsevier

Neuroscience

Volume 141, Issue 1, 2006, Pages 501-513
Neuroscience

Sensory system
Unique presynaptic and postsynaptic roles of Group II metabotropic glutamate receptors in the modulation of thalamic network activity

https://doi.org/10.1016/j.neuroscience.2006.03.060Get rights and content

Abstract

The thalamic reticular nucleus (TRN) is a sheet of GABAergic neurons that project to other TRN neurons and to associated thalamocortical relay nuclei. The TRN receives glutamatergic synaptic inputs from cortex as well as reciprocal inputs from the collaterals of thalamocortical neurons. In addition to ionotropic glutamate receptors, metabotropic glutamate receptors (mGluRs) are present in the TRN circuitry. Using whole cell voltage clamp recordings, we pharmacologically characterized unique pre- and postsynaptic functions for Group II mGluRs (mGluR 2 and mGluR 3) within the TRN circuitry in ferrets. mGluR 2 was found on presynaptic cortical axon terminals in the TRN, where it reduced glutamate release, while mGluR 3 acted postsynaptically on TRN cells to increase membrane conductance. Using miniature inhibitory postsynaptic current analysis, we also found that picrotoxin-sensitive intra-TRN GABA-mediated neurotransmission was not affected by administration of a Group II mGluR agonist, indicating that neither mGluR 2 nor 3 acts on presynaptic GABA-containing terminals within the TRN. Because strong corticothalamic activation is implicated in abnormal thalamic rhythms, we used extracellular recordings in the lateral geniculate nucleus to study the effect of Group II mGluR agonists upon these slow oscillations. We induced ∼3 Hz spike-and-wave discharge activity through corticothalamic stimulation, and found that such activity was reduced in the presence of the Group II mGluR agonist, (−)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268). These data indicate that Group II mGluR reduce the impact of corticothalamic excitation, and that they may be a useful target in the reduction of absence-like rhythms.

Section snippets

Slice preparation

Slices were prepared as previously described (Alexander and Godwin, 2005). Male ferrets older than postnatal day 42 were anesthetized with halothane and decapitated in accordance with procedures approved by the Wake Forest University Animal Care and Use Committee and in agreement with National Institutes of Health and United States Department of Agriculture guidelines. Every effort was made to minimize animal suffering, and the number of animals used was kept to a minimum. The brain was rapidly

Results

Data were collected with voltage clamp recordings from 73 cells in the visual sector of the TRN adjacent to the LGN (the perigeniculate nucleus), which had a mean resting membrane potential of −67.9±0.7 mV as measured in current clamp recordings. Eight LGN cells were studied using extracellular electrodes.

Discussion

MGluRs are active at several sites in the thalamus, where they perform unique functions in the control of membrane voltage and ongoing synaptic transmission. In this study, we have found that mGluR3 acts postsynaptically on TRN cells to reduce membrane resistance, while GluR2 acts on presynaptic corticothalamic axon terminals to reduce glutamate release. Moreover, we have found that mGluR2 is synaptically activated on cortical terminals in the TRN by 10 Hz train stimulation. We examined

Acknowledgments

This work was supported by EY11695; AA013246; AA011997; NS046222; Grant-In-Aid of Research from the National Academy of Sciences, administered by Sigma Xi, the Scientific Research Society.

References (91)

  • S.W. Hughes et al.

    Synchronized oscillations at alpha and theta frequencies in the lateral geniculate nucleus

    Neuron

    (2004)
  • D.J. Laurie et al.

    Cloning, distribution and functional expression of the human mGlu6 metabotropic glutamate receptor

    Neuropharmacology

    (1997)
  • K.H. Lee et al.

    Modulation of spindle oscillations by acetylcholine, cholecystokinin and 1S,3R-ACPD in the ferret lateral geniculate and perigeniculate nuclei in vitro

    Neuroscience

    (1997)
  • Z. Liu et al.

    Involvement of intrathalamic GABAB neurotransmission in the control of absence seizures in the rat

    Neuroscience

    (1992)
  • E. Mineff et al.

    Metabotropic glutamate receptors 2 and 3 expressed by astrocytes in rat ventrobasal thalamus

    Neurosci Lett

    (1999)
  • R.X. Moldrich et al.

    Astrocyte mGlu(2/3)-mediated cAMP potentiation is calcium sensitivestudies in murine neuronal and astrocyte cultures

    Neuropharmacology

    (2002)
  • V.M. Montero

    Attentional activation of the visual thalamic reticular nucleus depends on “top-down” inputs from the primary visual cortex via corticogeniculate pathway

    Brain Res

    (2000)
  • Y. Nakajima et al.

    Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate

    J Biol Chem

    (1993)
  • A. Neki et al.

    Pre- and postsynaptic localization of a metabotropic glutamate receptor, mGluR2, in the rat brainan immunohistochemical study with a monoclonal antibody

    Neurosci Lett

    (1996)
  • H. Ohishi et al.

    Distribution of the messenger RNA for a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat

    Neuroscience

    (1993)
  • R.S. Petralia et al.

    The metabotropic glutamate receptors, mGluR2 and mGluR3, show unique postsynaptic, presynaptic and glial localizations

    Neuroscience

    (1996)
  • D. Pinault et al.

    Thalamic reticular input to the rat visual thalamusa single fiber study using biocytin as an anterograde tracer

    Brain Res

    (1995)
  • T.E. Salt et al.

    Distinct presynaptic metabotropic receptors for L-AP4 and CCG1 on GABAergic terminalspharmacological evidence using novel alpha-methyl derivative mGluR antagonists, MAP4 and MCCG, in the rat thalamus in vivo

    Neuroscience

    (1995)
  • T.E. Salt et al.

    Modulation of sensory neurone excitatory and inhibitory responses in the ventrobasal thalamus by activation of metabotropic excitatory amino acid receptors

    Neuropharmacology

    (1995)
  • M. Steriade et al.

    The thalamus as a neuronal oscillator

    Brain Res

    (1984)
  • Y. Tanabe et al.

    A family of metabotropic glutamate receptors

    Neuron

    (1992)
  • J.P. Turner et al.

    Synaptic activation of the group I metabotropic glutamate receptor mGluR1 on the thalamocortical neurons of the rat dorsal lateral geniculate nucleus in vitro

    Neuroscience

    (2000)
  • J.P. Turner et al.

    Group II and III metabotropic glutamate receptors and the control of the nucleus reticularis thalami input to rat thalamocortical neurones in vitro

    Neuroscience

    (2003)
  • M. von Krosigk et al.

    Dynamic properties of corticothalamic excitatory postsynaptic potentials and thalamic reticular inhibitory postsynaptic potentials in thalamocortical neurons of the guinea-pig dorsal lateral geniculate nucleus

    Neuroscience

    (1999)
  • G.M. Alexander et al.

    Presynaptic inhibition of corticothalamic feedback by metabotropic glutamate receptors

    J Neurophysiol

    (2005)
  • T. Bal et al.

    Cortical feedback controls the frequency and synchrony of oscillations in the visual thalamus

    J Neurosci

    (2000)
  • A. Berent-Spillson et al.

    Protection against glucose-induced neuronal death by NAAG and GCP II inhibition is regulated by mGluR3

    J Neurochem

    (2004)
  • M.E. Bickford et al.

    GABAergic projection from the basal forebrain to the visual sector of the thalamic reticular nucleus in the cat

    J Comp Neurol

    (1994)
  • H. Blumenfeld et al.

    Corticothalamic inputs control the pattern of activity generated in thalamocortical networks

    J Neurosci

    (2000)
  • S.R. Bradley et al.

    Distribution and developmental regulation of metabotropic glutamate receptor 7a in rat brain

    J Neurochem

    (1998)
  • P.J. Conn et al.

    Pharmacology and functions of metabotropic glutamate receptors

    Annu Rev Pharmacol Toxicol

    (1997)
  • C.L. Cox et al.

    Glutamate inhibits thalamic reticular neurons

    J Neurosci

    (1999)
  • F. Crick

    Function of the thalamic reticular complexThe searchlight hypothesis

    Proc Natl Acad Sci U S A

    (1984)
  • J.B. Cucchiaro et al.

    Electron-microscopic analysis of synaptic input from the perigeniculate nucleus to the A-laminae of the lateral geniculate nucleus in cats

    J Comp Neurol

    (1991)
  • F.H. da Silva et al.

    Organization of thalamic and cortical alpha rhythmsspectra and coherences

    Electroencephalogr Clin Neurophysiol

    (1973)
  • A. Destexhe

    Spike-and-wave oscillations based on the properties of GABAB receptors

    J Neurosci

    (1998)
  • P. Fuentealba et al.

    Experimental evidence and modeling studies support a synchronizing role for electrical coupling in the cat thalamic reticular neurons in vivo

    Eur J Neurosci

    (2004)
  • D.W. Godwin et al.

    Ultrastructural localization suggests that retinal and cortical inputs access different metabotropic glutamate receptors in the lateral geniculate nucleus

    J Neurosci

    (1996)
  • D.W. Godwin et al.

    Metabotropic glutamate receptors switch visual response mode of lateral geniculate nucleus cells from burst to tonic

    J Neurophysiol

    (1996)
  • B. Granseth

    Dynamic properties of corticogeniculate excitatory transmission in the rat dorsal lateral geniculate nucleus in vitro

    J Physiol

    (2004)

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