Neuronal activity patterns in the mediodorsal thalamus and related cognitive circuits are modulated by metabotropic glutamate receptors.
Bottom Line: 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.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.
Affiliation: Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK. Electronic address: firstname.lastname@example.org.Show MeSH
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Mentions: We first assessed whether the Group II mGlu receptors could broadly disinhibit neuronal firing in the MD. Conveniently, spontaneously-firing MD neurones provided us with a background of excitation upon which inhibition could be visualised. Stimulation of either the PFC or amygdala was found to reduce the spontaneous firing of MD neurones, with local application of the Group II mGlu receptor orthosteric agonist LY354740 able to significantly reduce the extent of the evoked inhibition (PFC – 24% ± 10% of control; n = 6 from 5 rats; p < 0.05; amygdala – 45% ± 12% of control; n = 5 from 5 rats; p < 0.05; Fig. 1). The ability of the Group II mGlu receptors to reduce evoked inhibition in a thalamic nucleus is similar to that observed previously in the VB (Salt and Turner, 1998; Copeland et al., 2012). Therefore, we next sought to examine how Group II mGlu receptor activation may modulate characteristic thalamic activity patterns, short-latency and long-latency burst firing, in the MD.
Affiliation: Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK. Electronic address: email@example.com.