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

doi:10.1016/j.neuroscience.2003.08.014

Neuroscience

Volume 122, Issue 2, 2003, Pages 459-469

https://doi.org/10.1016/j.neuroscience.2003.08.014 Get rights and content

Abstract

Intracellular recordings were made from neurones in the thalamic reticular nucleus (TRN) and ventro-basal (VB) thalamus in slices of rat midbrain in vitro. Electrical stimulation of the medial lemniscus or TRN resulted in the generation of complex synaptic potentials containing disynaptic inhibitory post-synaptic potentials (IPSPs) in VB thalamocortical neurones. Analysis of the excitatory synaptic responses in TRN neurones indicates they can produce burst output response irrespective of the level of sub-threshold membrane potential. This suggests that network-evoked IPSPs in VB thalamocortical neurones occur following a burst of TRN action potentials. Using ionotropic glutamate receptor antagonists, the activation of these disynaptic events was blocked, and the monosynaptic IPSPs that resulted from the direct activation of the TRN could be isolated. The selective Group II agonists LY354740 (1–10 μM) and N-acetyl-aspartyl-glutamate (NAAG; 100–500 μM) both caused a reversible depression of these monosynaptic TRN IPSPs without any effect on membrane potential or input resistance. Likewise, the specific Group III agonist l-2-amino-4-phosphonobutanoate (10–500 μM), but not (RS)-4-phosphonophenylglycine (1 and 30 μM) also caused a reversible depression of these IPSPs, again without any effect on membrane potential or input resistance.

Thus, the IPSPs recorded in VB thalamocortical neurones, evoked by TRN activation, can be depressed by the activation of either Group II or III metabotropic glutamate receptors. This is consistent with the location of these receptor types on the presynaptic terminals of TRN axons in the VB thalamus. This raises the possibility that, during periods of intense excitatory activity, glutamate release could influence the release of GABA from TRN axon terminals in the thalamus. In addition, as NAAG is located in the axons and terminals arising from the TRN, there is the possibility that this dipeptide is also released by these terminals to control the release of GABA during periods of high activity in the TRN.

Section snippets

Preparation of brain slices

All experiments were carried out on rats of either sex in accordance with the U.K. Animals (Scientific Procedures) Act, 1986 and associated guidelines as approved by the Home Office to minimize their suffering. The number of animals used was kept to the minimum necessary to obtain statistically significant results. Rats (60–200 g) were anaesthetized with halothane (May & Baker, Dagenham, UK) and decapitated. Their brains were then rapidly removed and placed in ice-cold (1–3 °C) continuously

Effect of blocking glutamatergic synaptic transmission on synaptic potentials in the VB thalamus: the isolation of IPSPs of TRN origin

Under control conditions, the nature of the synaptic potentials generated by activation of ML and the cortical and TRN inputs were variable depending upon the integrity of the connectivity that was maintained following tissue slicing. Synaptic potentials varied considerably, and could either be dominated by excitatory (data not shown) or inhibitory events (Fig. 1). As a general rule, those events made up predominantly of excitatory events proved to have little underlying contribution from

Main conclusions

The main conclusions of this study are:

1. The normal synaptic activation of the TRN can result in burst firing and the generation of temporally summated IPSPs recorded in TC neurones.

2. The activation of cortical/TC excitatory inputs is able to drive the burst firing of TRN neurones when inhibition is blocked, but that its temporal character is dependent on membrane potential.

3. The magnitude of these TRN IPSPs can be controlled by the activation of either Group II and/or Group III mGlu

Acknowledgements

We wish to thank Dr. I. Tarnawa, Institute for Drug Research, Budapest for the GYKI 52466, Dr. W. Fröstl, Ciba-Geigy/Novartis for the CGP55845A; and Lilly Research for LY354740 and LY341495. This work was supported by the Wellcome Trust.

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

Abstract

Section snippets

Preparation of brain slices

Effect of blocking glutamatergic synaptic transmission on synaptic potentials in the VB thalamus: the isolation of IPSPs of TRN origin

Main conclusions

Acknowledgements

Neuropharmacology

Neuroscience

Neuroscience

Neuroscience

Eur J Pharmacol

Neuropharmacology

Prog Brain Res

J Chem Neuroanat

Brain Res

Neuron

Neurosci Lett

Brain Res

Neuroscience

Neuroscience

J Biol Chem

Neuroscience

Neuroscience

Neuroscience

Neuroscience

Neuroscience

Neuropharmacology

Brain Res

Prog Neurobiol

Neuroscience

Eur J Pharmacol (Mol Pharmacol Sec)

Neuroscience

Intrinsic properties of nucleus reticularis thalami neurones of the rat studied in vitro

J Physiol (Lond)

Mechanisms of oscillatory activity in guinea-pig nucleus reticularis thalami in vitroa mammalian pacemaker

J Physiol (Lond)

Anatomic, intrinsic, and synaptic properties of dorsal and ventral division neurons in rat medial geniculate body

J Neurophysiol

Pharmacology and functions of metabotropic glutamate receptors

Annu Rev Pharmacol Toxicol

A novel metabotropic glutamate receptor expressed in the retina and olfactory bulb

J Neurosci