NEURAL CIRCUITS

A stand-out loop

The paraventricular thalamus (PVT) is involved in arousal and valence processing. However, how this structure is functionally organized is not clear. Gao et al. molecularly, anatomically and functionally characterized two subpopulations of PVT neurons in mice, one of which forms a thalamo-corticothalamic loop with the infralimbic cortex (IL) that regulates arousal.

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Through RNA in situ hybridization, the authors examined the expression of transcripts encoding the dopamine D2 receptor (D2R) along the anteroposterior axis of the PVT. The density of Drd2-positive cells was higher in the posterior PVT (pPVT) than in the anterior PVT (aPVT). Notably, the authors found that, whereas D2R+ neurons (which the authors called type I neurons), project to the prelimbic cortex, D2R neurons (called type II neurons) project to the IL. Thus, these molecularly defined cell classes are also anatomically distinct.

The authors imaged the Ca2+ responses of these two neuron types as mice were exposed to various salient stimuli, including aversive stimuli (such as a tail shock) and rewarding stimuli (such as a female mouse). Type I neurons showed increased and decreased Ca2+ fluorescence in response to aversive and rewarding stimuli, respectively. By contrast, aversive and rewarding stimuli both reduced Ca2+ fluorescence in type II neuronal cell bodies — and their terminals in the IL — suggesting that type II neurons signal salience to the IL.

Labelled projections from the prelimbic cortex and IL were observed to preferentially innervate the pPVT and aPVT, respectively. In support of a PVT–IL–PVT loop, Ca2+ fluorescence in IL neurons projecting back to the PVT (ILPVT neurons) was increased by photostimulation of PVT inputs to the IL (PVTIL neurons). Moreover, ILPVT neurons exhibited reductions in Ca2+ fluorescence when mice were exposed to aversive or rewarding stimuli. Optogenetic activation of PVTIL neurons attenuated the reductions in IL Ca2+ fluorescence associated with aversive or rewarding stimuli, whereas light suppression of PVTIL neurons did not affect salience-induced IL responses. Therefore, salience inhibits activity in this PVT–IL–PVT loop.

The authors reasoned that this loop could be involved in PVT regulation of arousal. Indeed, chemogenetic activation of type II neurons before the onset of the dark period (when mice are typically more awake) reduced wakefulness and promoted non-rapid-eye-movement sleep. Spontaneous or tail-shock-induced dilation of the pupils — a sign of arousal — was associated with reduced Ca2+ fluorescence in ILPVT neurons. Photostimulation of the ILPVT neurons attenuated pupil-dilation responses to tail shocks, suggesting that the IL regulates salience-induced arousal.

“aversive and rewarding stimuli both reduced Ca2+ fluorescence in type II neuronal cell bodies”

Overall, this study reveals a PVT–IL–PVT loop that signals salience and regulates arousal.

References

Original article

  1. Gao, C. et al. Two genetically, anatomically and functionally distinct cell types segregate across anteroposterior axis paraventricular thalamus. Nat. Neurosci. https://doi.org/10.1038/s41593-019-0572-3 (2020)

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Correspondence to Natasha Bray.

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Bray, N. A stand-out loop. Nat Rev Neurosci 21, 120 (2020). https://doi.org/10.1038/s41583-020-0267-5

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