Yinqing Li published 'Distinct subnetworks of the thalamic reticular nucleus' in Nature.

Date:2020-07-22

On 22 July 2020, Yinqing Li published 'Distinct subnetworks of the thalamic reticular nucleus' in Nature.

Abstract

The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, regulates thalamocortical interactions that are critical for sensory processing, attention and cognition1,2,3,4,5. TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders6,7,8,9. However, little is known about the organizational principles that underlie its divergent functions. Here we performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that cellular heterogeneity in the TRN is characterized by a transcriptomic gradient of two negatively correlated gene-expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core or shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections with the functionally distinct first-order and higher-order thalamic nuclei to form molecularly defined TRN–thalamus subnetworks. Selective perturbation of the two subnetworks in vivo revealed their differential role in regulating sleep. In sum, our study provides a comprehensive atlas of TRN neurons at single-cell resolution and links molecularly defined subnetworks to the functional organization of thalamocortical circuits.

Reference

1. Dong, P. et al. A novel cortico-intrathalamic circuit for flight behavior. Nat. Neurosci22, 941–949 (2019).

2. Halassa, M. M. et al. State-dependent architecture of thalamic reticular subnetworks. Cell 158, 808–821 (2014).

3. McAlonan, K., Cavanaugh, J. & Wurtz, R. H. Attentional modulation of thalamic reticular neurons. J. Neurosci26, 4444–4450 (2006).

4. Pinault, D. The thalamic reticular nucleus: structure, function and concept. Brain Res. Brain Res. Rev46, 1–31 (2004).

5. Sherman, S. M. & Guillery, R. W. The role of the thalamus in the flow of information to the cortex. Phil. Trans. R. Soc. Lond. B 357, 1695–1708 (2002).

6. Ferrarelli, F. & Tononi, G. The thalamic reticular nucleus and schizophrenia. Schizophr. Bull37, 306–315 (2011).

7. Krol, A., Wimmer, R. D., Halassa, M. M. & Feng, G. Thalamic reticular dysfunction as a circuit endophenotype in neurodevelopmental disorders. Neuron 98, 282–295 (2018).

8. Saletin, J. M., Coon, W. G. & Carskadon, M. A. Stage 2 sleep EEG sigma activity and motor learning in childhood ADHD: a pilot study. J. Clin. Child Adolesc. Psychol46, 188–197 (2017).

9. Steullet, P. et al. The thalamic reticular nucleus in schizophrenia and bipolar disorder: role of parvalbumin-expressing neuron networks and oxidative stress. Mol. Psychiatry 23, 2057–2065 (2018).