Two dynamically distinct circuits drive inhibition in the sensory thalamus
Authors: Barry W Connors
Bettina Voelcker
Julia B Zaltsman
Tanya R Stevens
Rosa I Martinez-Garcia
Scott J Cruikshank
Saundra L Patrick
Journal: Nature (2020)
Discipline: Multidisciplinary
Keywords: Thalamus; Thalamocortical neurons; Thalamic reticular nucleus; Somatosensory circuits; Visual circuits
Affiliations: Department of Neuroscience, Division of Biology and Medicine, Brown University, Providence, RI, USA., Department of Molecular Biology, Cell Biology, and Biochemistry, Division of Biology and Medicine, Brown University, Providence, RI, USA., Robert J. & Nancy D. Carney Institute for Brain Science, Brown University, Providence, RI, USA., Center for Neural Science, New York University, New York, NY, USA., Department of Neuroscience, Division of Biology and Medicine, Brown University, Providence, RI, USA. ., The UAB Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL, USA. ., UAB Comprehensive Neuroscience Center, University of Alabama at Birmingham, Birmingham, AL, USA. ., Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA. .

Abstract:  Most sensory information destined for the neocortex is relayed through the thalamus, where considerable transformation occurs1,2. One means of transformation involves interactions between excitatory thalamocortical neurons that carry data to the cortex and inhibitory neurons of the thalamic reticular nucleus (TRN) that regulate the flow of those data3-6. Although the importance of the TRN has long been recognised7-9, understanding of its cell types, their organization and their functional properties has lagged behind that of the thalamocortical systems they control. Here we address this by investigating the somatosensory and visual circuits of the TRN in mice. In the somatosensory TRN we observed two groups of genetically defined neurons that are topographically segregated and physiologically distinct, and that connect reciprocally with independent thalamocortical nuclei through dynamically divergent synapses. Calbindin-expressing cells-located in the central core-connect with the ventral posterior nucleus, the primary somatosensory thalamocortical relay. By contrast, somatostatin-expressing cells-which reside along the surrounding edges of the TRN-synapse with the posterior medial thalamic nucleus, a higher-order structure that carries both top-down and bottom-up information10-12. The two TRN cell groups process their inputs in pathway-specific ways. Synapses from the ventral posterior nucleus to central TRN cells transmit rapid excitatory currents that depress deeply during repetitive activity, driving phasic spike output. Synapses from the posterior medial thalamic nucleus to edge TRN cells evoke slower, less depressing excitatory currents that drive more persistent spiking. Differences in the intrinsic physiology of TRN cell types, including state-dependent bursting, contribute to these output dynamics. The processing specializations of these two somatosensory TRN subcircuits therefore appear to be tuned to the signals they carry-a primary central subcircuit tuned to discrete sensory events, and a higher-order edge subcircuit tuned to temporally distributed signals integrated from multiple sources. The structure and function of visual TRN subcircuits closely resemble those of the somatosensory TRN. These results provide insights into how subnetworks of TRN neurons may differentially process distinct classes of thalamic information. 

Retracted: No

PubPeer comments:
 https: twitter.com HuguenardLab status 1288251239969329153 , 
 **Previous papers demonstrating diversity of structure and function in the thalamic reticular nucleus (TRN)** Molecular diversity and gradients within TRN, including somatostatin, calbindin, and parvalbumin (Zhang, 2006; Oda et al., 2007; Baldauf, 2010; Ahrens et al., 2015; Clemente-Perez et al., 2017) Burst firing differences (Lee et al., 2007; Kimura et al., 2012; Kimura and Imbe, 2015; Clemente-Perez et al., 2017). Anatomical heterogeneity (Spreafico et al., 1988, 1991; Cox et al., 1996; Pinault and Deschu02c6nes, 1998) Functional differences (Cox et al., 1997; Mistry et al., 2008; Ahrens et al., 2015; Crabtree, 2018) Distinct first order vs higher order connectivity (Fitzgibbon, 2007; Lam and Sherman, 2007; Kimura et al., 2012; Kimura and Imbe, 2015; Zhang et al., 2015; Clemente-Perez et al., 2017) Chemical synaptic connectivity between TRN cells, rat and mouse (Spreafico et al., 1988; Zhang et al., 1997; Huntsman et al., 1999, 1999; Sohal and Huguenard, 2003; Zhang and Jones, 2004; Deleuze and Huguenard, 2006; Lam et al., 2006; Schofield et al., 2009) Note, there is evidence that chemical, not electrical, synapses are less prominent in mouse than other species (Landisman et al., 2002; Long et al., 2004; Cruikshank et al., 2010; Hou et al., 2016) Roles for RTN heterogeneity in regulating sleep spindles (Fernandez et al., 2018; Vantomme et al., 2019) Important reviews (Pinault, 2004; Crabtree, 2018) Finally, please note that RTN is highly heterogenous between species (Arcelli et al., 1997), including presumably humans, and that the first order higher order core and shell structure of mouse may not be a feature of higher species, such as felines (Crabtree, 1996). **Bibliography** Ahrens S, Jaramillo S, Yu K, Ghosh S, Hwang G-R, Paik R, Lai C, He M, Huang ZJ, Li B (2015) ErbB4 regulation of a thalamic reticular nucleus circuit for sensory selection. 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 I find the results of Martinez-Garcia and colleagues to be highly novel. Yes, as pointed out, there is lots of evidence for TRN neuronal heterogeneity and there is recent work by the Luthi lab indicating that the neuronal properties in distinct TRN sectors uniquely control sleep spindles. But this paper makes a very strong case that there are completely independent circuits WITHIN a given TRN sector that form interconnections with distinct thalamic nuclei. Perhaps those of us familiar with all the previous work could have put the pieces together and made an educated guess for their existence, but its one thing to speculate, and quite another to provide convincing data. Does this paper provide sufficient originality and importance to be published in a u201cpremieru201d scientific journal? I would say yes, but ultimately these are decisions that are in the hands of editors and a small group of reviewers and I donu2019t think the authors have to justify the decisions made by others. ,