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Neuronal activity patterns in the mediodorsal thalamus and related cognitive circuits are modulated by metabotropic glutamate receptors.

Copeland, CS; Neale, SA; Salt, TE; (2015) Neuronal activity patterns in the mediodorsal thalamus and related cognitive circuits are modulated by metabotropic glutamate receptors. Neuropharmacology , 92 16 - 24. 10.1016/j.neuropharm.2014.12.031. Green open access

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Abstract

The mediodorsal thalamus (MD) likely plays an important role in cognition as it receives abundant afferent connections from the amygdala and prefrontal cortex (PFC). Indeed, disturbed activity within the MD is thought to precipitate cognitive deficits associated with schizophrenia. As compounds acting at the Group II metabotropic glutamate (mGlu) receptors (subtypes mGlu2/mGlu3) have efficacy in animal models of schizophrenia, we investigated whether a Group II agonist and an mGlu2 positive allosteric modulator (PAM) could modulate MD activity. Extracellular single-unit recordings were made in vivo from MD neurones in anaesthetised rats. Responses were elicited by electrical stimulation of the PFC and/or amygdala, with Group II compounds locally applied as required. The Group II agonist reduced inhibition evoked in the MD: an effect manifested as an increase in short-latency responses, and a decrease in long-latency burst-firing. This disinhibitory action of the Group II receptors in the MD represents a mechanism of potential therapeutic importance as increased inhibition in the MD has been associated with cognitive deficit-onset. Furthermore, as co-application of the mGlu2 PAM did not potentiate the Group II agonist effects in the MD, we suggest that the Group II disinhibitory effect is majority-mediated via mGlu3. This heterogeneity in Group II receptor thalamic physiology bears consequence, as compounds active exclusively at the mGlu2 subtype are unlikely to perturb maladapted MD firing patterns associated with cognitive deficits, with activity at mGlu3 receptors possibly more appropriate. Indeed, polymorphisms in the mGlu3, but not the mGlu2, gene have been detected in patients with schizophrenia.

Type: Article
Title: Neuronal activity patterns in the mediodorsal thalamus and related cognitive circuits are modulated by metabotropic glutamate receptors.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuropharm.2014.12.031
Publisher version: http://dx.doi.org/10.1016/j.neuropharm.2014.12.031
Language: English
Additional information: Copyright © 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Burst firing, Egluetad (PubChem CID 156665), Mediodorsal thalamus, Metabotropic glutamate receptor, N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl)pyrid-3-ylmethylamine (PubChem CID 9825084), N-Methylaspartate (PubChem CID 22880), Schizophrenia, Synaptic inhibition
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1465514
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