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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 - Neuropharmacology (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK. Electronic address: carolinecopeland@gmail.com.

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Group II mGlu receptor activation decreases evoked burst firing in the VB. i Vibrissal deflection schematic and recording site location for the VB electrode. ii Illustrative raster display and PSTH of a VB neuron (CVB78c) displaying both tonic and burst firing in response to vibrissal deflection. 20 ms bins over 30 trials. iii PSTHs of burst firing responses of the same VB neurone to vibrissal deflection under normal conditions, upon Group II agonist application alone, upon Group II agonist and mGlu2 PAM co-application, and recovery. Burst spikes, orange; tonic short-latency (8–50 ms) spikes, grey; total long-latency (300–1000 ms) spikes, black; 50 ms bins over 30 trials. iv Bars represent the mean % response (±SEM) under the same conditions (n = 5). *p < 0.05 when compared to control, unless otherwise indicated. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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fig4: Group II mGlu receptor activation decreases evoked burst firing in the VB. i Vibrissal deflection schematic and recording site location for the VB electrode. ii Illustrative raster display and PSTH of a VB neuron (CVB78c) displaying both tonic and burst firing in response to vibrissal deflection. 20 ms bins over 30 trials. iii PSTHs of burst firing responses of the same VB neurone to vibrissal deflection under normal conditions, upon Group II agonist application alone, upon Group II agonist and mGlu2 PAM co-application, and recovery. Burst spikes, orange; tonic short-latency (8–50 ms) spikes, grey; total long-latency (300–1000 ms) spikes, black; 50 ms bins over 30 trials. iv Bars represent the mean % response (±SEM) under the same conditions (n = 5). *p < 0.05 when compared to control, unless otherwise indicated. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Mentions: In quiescent MD neurones in which long-latency burst-firing could be evoked, local application of the Group II agonist was also able to significantly reduce the proportion of burst activity evoked upon electrical stimulation of the PFC without affecting the overall magnitude of the response (Control – total number of spikes: 100% ± 0%; proportion of spikes in bursts: 76% ± 5%; Group II agonist – total number of spikes: 93% ± 5%; proportion of spikes in bursts: 57% ± 2%; n = 5 from 4 rats, p < 0.05; Fig. 3). This decrease in the proportion of burst firing is likely due to Group II mGlu receptors localized on TRN terminals reducing GABAergic transmission and the subsequent hyperpolarization of MD neurones (Llinas and Jahnsen, 1982; Jahnsen and Llinas, 1984; Ohara and Lieberman, 1993; Varga et al., 2002). However, in the same population of neurones, co-application of the mGlu2 PAM did not potentiate the Group II agonist effect on evoked burst activity (Group II agonist plus mGlu2 PAM – total number of spikes: 92% ± 11% of control; proportion of spikes in bursts: 60% ± 5%; n = 5 from 4 rats; p > 0.05; Fig. 3). In contrast, in quiescent VB neurones in which burst-firing could be evoked, local application of the Group II agonist was able to significantly reduce burst activity evoked upon principal vibrissa deflection without affecting the magnitude of the overall neuronal response (Control – total number of spikes: 100% ± 0%; proportion of spikes in bursts 66% ± 7%; Group II agonist – total number of spikes: 88% ± 28%; proportion of spikes in bursts 51% ± 9%; n = 5 from 5 rats, p < 0.05; Fig. 4); an effect that was potentiated upon co-application of the mGlu2 PAM (Group II agonist plus mGlu2 PAM – total number of spikes: 114% ± 23% of control; proportion of spikes in bursts 38% ± 9%, n = 5 from 5 rats, p < 0.05; Fig. 4). These data provide further evidence that whilst there is an mGlu2 component to the Group II mGlu receptor effect in the VB, there is no such component in the MD.


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

Copeland CS, Neale SA, Salt TE - Neuropharmacology (2015)

Group II mGlu receptor activation decreases evoked burst firing in the VB. i Vibrissal deflection schematic and recording site location for the VB electrode. ii Illustrative raster display and PSTH of a VB neuron (CVB78c) displaying both tonic and burst firing in response to vibrissal deflection. 20 ms bins over 30 trials. iii PSTHs of burst firing responses of the same VB neurone to vibrissal deflection under normal conditions, upon Group II agonist application alone, upon Group II agonist and mGlu2 PAM co-application, and recovery. Burst spikes, orange; tonic short-latency (8–50 ms) spikes, grey; total long-latency (300–1000 ms) spikes, black; 50 ms bins over 30 trials. iv Bars represent the mean % response (±SEM) under the same conditions (n = 5). *p < 0.05 when compared to control, unless otherwise indicated. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
© Copyright Policy - CC BY
Related In: Results  -  Collection

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fig4: Group II mGlu receptor activation decreases evoked burst firing in the VB. i Vibrissal deflection schematic and recording site location for the VB electrode. ii Illustrative raster display and PSTH of a VB neuron (CVB78c) displaying both tonic and burst firing in response to vibrissal deflection. 20 ms bins over 30 trials. iii PSTHs of burst firing responses of the same VB neurone to vibrissal deflection under normal conditions, upon Group II agonist application alone, upon Group II agonist and mGlu2 PAM co-application, and recovery. Burst spikes, orange; tonic short-latency (8–50 ms) spikes, grey; total long-latency (300–1000 ms) spikes, black; 50 ms bins over 30 trials. iv Bars represent the mean % response (±SEM) under the same conditions (n = 5). *p < 0.05 when compared to control, unless otherwise indicated. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Mentions: In quiescent MD neurones in which long-latency burst-firing could be evoked, local application of the Group II agonist was also able to significantly reduce the proportion of burst activity evoked upon electrical stimulation of the PFC without affecting the overall magnitude of the response (Control – total number of spikes: 100% ± 0%; proportion of spikes in bursts: 76% ± 5%; Group II agonist – total number of spikes: 93% ± 5%; proportion of spikes in bursts: 57% ± 2%; n = 5 from 4 rats, p < 0.05; Fig. 3). This decrease in the proportion of burst firing is likely due to Group II mGlu receptors localized on TRN terminals reducing GABAergic transmission and the subsequent hyperpolarization of MD neurones (Llinas and Jahnsen, 1982; Jahnsen and Llinas, 1984; Ohara and Lieberman, 1993; Varga et al., 2002). However, in the same population of neurones, co-application of the mGlu2 PAM did not potentiate the Group II agonist effect on evoked burst activity (Group II agonist plus mGlu2 PAM – total number of spikes: 92% ± 11% of control; proportion of spikes in bursts: 60% ± 5%; n = 5 from 4 rats; p > 0.05; Fig. 3). In contrast, in quiescent VB neurones in which burst-firing could be evoked, local application of the Group II agonist was able to significantly reduce burst activity evoked upon principal vibrissa deflection without affecting the magnitude of the overall neuronal response (Control – total number of spikes: 100% ± 0%; proportion of spikes in bursts 66% ± 7%; Group II agonist – total number of spikes: 88% ± 28%; proportion of spikes in bursts 51% ± 9%; n = 5 from 5 rats, p < 0.05; Fig. 4); an effect that was potentiated upon co-application of the mGlu2 PAM (Group II agonist plus mGlu2 PAM – total number of spikes: 114% ± 23% of control; proportion of spikes in bursts 38% ± 9%, n = 5 from 5 rats, p < 0.05; Fig. 4). These data provide further evidence that whilst there is an mGlu2 component to the Group II mGlu receptor effect in the VB, there is no such component in the MD.

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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK. Electronic address: carolinecopeland@gmail.com.

Show MeSH
Related in: MedlinePlus