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Thalamic subnetworks as units of function

Nature Neuroscience volume 25, pages 140–153 (2022)Cite this article

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Abstract

The thalamus engages in various functions including sensory processing, attention, decision making and memory. Classically, this diversity of function has been attributed to the nuclear organization of the thalamus, with each nucleus performing a well-defined function. Here, we highlight recent studies that used state-of-the-art expression profiling, which have revealed gene expression gradients at the single-cell level within and across thalamic nuclei. These gradients, combined with anatomical tracing and physiological analyses, point to previously unappreciated heterogeneity and redefine thalamic units of function on the basis of unique input–output connectivity patterns and gene expression. We propose that thalamic subnetworks, defined by the intersection of genetics, connectivity and computation, provide a more appropriate level of functional description; this notion is supported by behavioral phenotypes resulting from appropriately tailored perturbations. We provide several examples of thalamic subnetworks and suggest how this new perspective may both propel progress in basic neuroscience and reveal unique targets with therapeutic potential.

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Fig. 1: Distinct thalamic nuclei in rodents.
Fig. 2: From thalamic nuclei to subnetworks.
Fig. 3: Diversity of thalamic neurons.
Fig. 4: Six genes can be used combinatorially to define thalamic nuclei.
Fig. 5: Single-cell heterogeneity of thalamic neurons.
Fig. 6: Subnetworks in the thalamus.
Fig. 7: From scRNA-seq to three distinct PF subpopulations.

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References

  1. Jones, E. G. The Thalamus (Plenum, 1985).

  2. Sherman, S. M. & Guillery, R. W. Exploring the Thalamus and its Role in Cortical Function (MIT Press, 2006).

  3. Jones, E. G. The Thalamus (Cambridge Univ. Press, 2007).

  4. Crabtree, J. W. Functional diversity of thalamic reticular subnetworks. Front. Syst. Neurosci. 12, 41 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hubel, D. H. & Wiesel, T. N. Early exploration of the visual cortex. Neuron 20, 401–412 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Nakajima, M. & Halassa, M. M. Thalamic control of functional cortical connectivity. Curr. Opin. Neurobiol. 44, 127–131 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Halassa, M. M. & Sherman, S. M. Thalamocortical circuit motifs: a general framework. Neuron 103, 762–770 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Guillery, R. W. & Sherman, S. M. Thalamic relay functions and their role in corticocortical communication: generalizations from the visual system. Neuron 33, 163–175 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Briggs, F. & Usrey, W. M. Emerging views of corticothalamic function. Curr. Opin. Neurobiol. 18, 403–407 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sommer, M. A. The role of the thalamus in motor control. Curr. Opin. Neurobiol. 13, 663–670 (2003).

    Article  CAS  PubMed  Google Scholar 

  11. Haber, S. N. & Calzavara, R. The cortico-basal ganglia integrative network: the role of the thalamus. Brain Res. Bull. 78, 69–74 (2009).

    Article  PubMed  Google Scholar 

  12. Jankowski, M. M. et al. The anterior thalamus provides a subcortical circuit supporting memory and spatial navigation. Front. Syst. Neurosci. 7, 45 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Saalmann, Y. B. Intralaminar and medial thalamic influence on cortical synchrony, information transmission and cognition. Front. Syst. Neurosci. 8, 83 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Roy, D. S. et al. Anterior thalamic dysfunction underlies cognitive deficits in a subset of neuropsychiatric disease models. Neuron 109, 2590–2603 (2021).

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pinault, D. The thalamic reticular nucleus: structure, function and concept. Brain Res. Rev. 46, 1–31 (2004).

    Article  PubMed  Google Scholar 

  17. Li, Y. et al. Distinct subnetworks of the thalamic reticular nucleus. Nature 583, 819–824 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cembrowski, M. S. & Spruston, N. Heterogeneity within classical cell types is the rule: lessons from hippocampal pyramidal neurons. Nat. Rev. Neurosci. 20, 193–204 (2019).

    Article  CAS  PubMed  Google Scholar 

  19. Romanov, R. A., Alpar, A., Hokfelt, T. & Harkany, T. Unified classification of molecular, network, and endocrine features of hypothalamic neurons. Annu. Rev. Neurosci. 42, 1–26 (2019).

    Article  CAS  PubMed  Google Scholar 

  20. Martin, A. et al. A spatiomolecular map of the striatum. Cell Rep. 29, 4320–4333 (2019).

    Article  PubMed  Google Scholar 

  21. Zeng, H. & Sanes, J. R. Neuronal cell-type classification: challenges, opportunities and the path forward. Nat. Rev. Neurosci. 18, 530–546 (2017).

    Article  CAS  PubMed  Google Scholar 

  22. von Kolliker, A. Handbuch der Gewebelehre des Menschen (W. Engelmann, 1896).

  23. Guillery, R. W. A study of Golgi preparations from the dorsal lateral geniculate nucleus of the adult cat. J. Comp. Neurol. 128, 21–49 (1966).

    Article  CAS  PubMed  Google Scholar 

  24. Tello, F. Disposicion macroscopica y estructura del cuerpo geniculado externo. Trabajos Lab. Invest. Biol. Madr. 3, 39–62 (1904).

    Google Scholar 

  25. Szentagothai, J., Hamori, J. & Tombol, T. Degeneration and electron microscopic analysis of the synaptic glomeruli in the lateral geniculate body. Exp. Brain Res. 2, 283–301 (1966).

    Article  CAS  PubMed  Google Scholar 

  26. Tombol, T. Two types of short axon (Golgi 2nd) interneurons in the specific thalamic nuclei. Acta Morphol. Acad. Sci. Hung. 17, 285–297 (1969).

    CAS  PubMed  Google Scholar 

  27. Clasca, F., Rubio-Garrido, P. & Jabaudon, D. Unveiling the diversity of thalamocortical neuron subtypes. Eur. J. Neurosci. 35, 1524–1532 (2012).

    Article  PubMed  Google Scholar 

  28. Cajal, S. R. Y. Histologie du Systeme Nerveaux de l’Homme et des Vertebres (Maloine, 1911).

  29. Spreafico, R., Battaglia, G. & Frassoni, C. The reticular thalamic nucleus (RTN) of the rat: cytoarchitectural, Golgi, immunocytochemical, and horseradish peroxidase study. J. Comp. Neurol. 304, 478–490 (1991).

    Article  CAS  PubMed  Google Scholar 

  30. Yen, C. T., Hendry, S. H. C. & Jones, E. G. The morphology of physiologically identified GABAergic neurons in the somatic sensory part of the thalamic reticular nucleus in the cat. J. Neurosci. 5, 2254–2268 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Deleuze, C. & Huguenard, J. R. Distinct electrical and chemical connectivity maps in the thalamic reticular nucleus: potential roles in synchronization and sensation. J. Neurosci. 26, 8633–8645 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lorente de No, R. Cerebral Cortex: Architecture, Intracortical Connections, Motor Projections (Oxford Univ. Press, 1938).

  33. Jones, E. G. Thalamic organization and function after Cajal. Prog. Brain Res. 136, 333–357 (2002).

    Article  CAS  PubMed  Google Scholar 

  34. Abramson, B. P. & Chalupa, L. M. The laminar distribution of cortical connections with the tecto- and cortico-recipient zones in the cat’s lateral posterior nucleus. Neuroscience 15, 81–95 (1985).

    Article  CAS  PubMed  Google Scholar 

  35. Tong, L. & Spear, P. D. Single thalamic neurons project to both lateral suprasylvian visual cortex and area 17: a retrograde fluorescent double-labeling study. J. Comp. Neurol. 246, 254–264 (1986).

    Article  CAS  PubMed  Google Scholar 

  36. Rockland, K. S., Andresen, J., Cowie, R. J. & Robinson, D. L. Single axon analysis of pulvinocortical connections to several visual areas in the macaque. J. Comp. Neurol. 406, 221–250 (1999).

    Article  CAS  PubMed  Google Scholar 

  37. Patel, N. C. & Bickford, M. E. Synaptic targets of cholinergic terminals in the pulvinar nucleus of the cat. J. Comp. Neurol. 387, 266–278 (1997).

    Article  CAS  PubMed  Google Scholar 

  38. Colonnier, M. & Guillery, R. W. Synaptic organization in the lateral geniculate nucleus of the monkey. Z. für Zellforsch. 62, 333–355 (1964).

    Article  CAS  Google Scholar 

  39. Ferster, D. & LeVay, S. The axonal arborizations of lateral geniculate neurons in the striate cortex of the cat. J. Comp. Neurol. 182, 923–944 (1978).

    Article  CAS  PubMed  Google Scholar 

  40. Turner, J. P., Anderson, C. M., Williams, S. R. & Crunelli, V. Morphology and membrane properties of neurones in the cat ventrobasal thalamus in vitro. J. Physiol. 505, 707–726 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bartlett, E. L. & Smith, P. H. Anatomical, intrinsic, and synaptic properties of dorsal and ventral division neurons in the rat medial geniculate body. J. Neurophysiol. 81, 1999–2016 (1999).

    Article  CAS  PubMed  Google Scholar 

  42. Landisman, C. E. & Connors, B. W. VPM and PoM nuclei of the rat somatosensory thalamus: intrinsic neuronal properties and corticothalamic feedback. Cereb. Cortex 17, 2853–2865 (2007).

    Article  PubMed  Google Scholar 

  43. Aguilar, J., Morales-Botello, M. L. & Foffani, G. Tactile responses of hindpaw, forepaw and whisker neurons in the thalamic ventrobasal complex of anesthetized rats. Eur. J. Neurosci. 27, 378–387 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Phillips, J. W. et al. A repeated molecular architecture across thalamic pathways. Nat. Neurosci. 22, 1925–1935 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Llinas, R. R. & Jahnsen, H. Electrophysiology of mammalian thalamic neurones in vitro. Nature 297, 406–408 (1982).

    Article  CAS  PubMed  Google Scholar 

  46. Jahnsen, H. & Llinas, R. R. Electrophysiological properties of guinea-pig thalamic neurons: an in vitro study. J. Physiol. 349, 205–226 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Jahnsen, H. & Llinas, R. R. Ionic basis for the electroresponsiveness and oscillatory properties of guinea-pig thalamic neurons in vitro. J. Physiol. 349, 227–247 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Li, J., Bickford, M. E. & Guido, W. Distinct firing properties of higher order thalamic relay neurons. J. Neurophysiol. 90, 291–299 (2003).

    Article  CAS  PubMed  Google Scholar 

  49. Smith, P. H., Bartlett, E. L. & Kowalkowski, A. Unique combination of anatomy and physiology in cells of the rat paralaminar thalamic nuclei adjacent to the medial geniculate body. J. Comp. Neurol. 496, 314–334 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  50. O’hara, P. T., Lieberman, A. R., Hunt, S. P. & Wu, J. Y. Neural elements containing glutamic acid decarboxylase (GAD) in the dorsal lateral geniculate nucleus of the rat: immunohistochemical studies by light and electron microscopy. Neuroscience 8, 189–212 (1983).

    Article  Google Scholar 

  51. Parent, A. & Butcher, L. L. Organization and morphologies of acetylcholinesterase-containing neurons in the thalamus and hypothalamus of the rat. J. Comp. Neurol. 170, 205–226 (1976).

    Article  PubMed  Google Scholar 

  52. Wamsley, J. K., Zarbin, M., Birdsall, N. & Kuhar, M. J. Muscarinic cholinergic receptors: autoradiographic localization of high and low affinity agonist binding sites. Brain Res. 200, 1–12 (1980).

    Article  CAS  PubMed  Google Scholar 

  53. Jones, E. G. Distribution patterns of individual medial lemniscal axons in the ventrobasal complex of the monkey thalamus. J. Comp. Neurol. 215, 1–16 (1983).

    Article  CAS  PubMed  Google Scholar 

  54. Swanson, L. W. & Hartman, B. K. The central adrenergic system: an immunofluorescence study of the location of cell bodies and their efferent connections in the rat utilizing dopamine-β-hydroxylase as a marker. J. Comp. Neurol. 163, 467–506 (1975).

    Article  CAS  PubMed  Google Scholar 

  55. Kromer, L. F. & Moore, R. Y. A study of the organization of the locus coeruleus projections to the lateral geniculate nuclei in the albino rat. Neuroscience 5, 255–271 (1980).

    Article  CAS  PubMed  Google Scholar 

  56. Hokfelt, T., Fuxe, K., Goldstein, M. & Johansson, O. Immunohistochemical evidence for the existence of adrenaline neurons in the rat brain. Brain Res. 66, 235–251 (1974).

    Article  CAS  Google Scholar 

  57. Lindvall, O. & Bjorklund, A. The organization of the ascending catecholamine neuron systems in the rat brain as revealed by the glyoxylic acid fluorescence method. Acta Physiol. Scand. Suppl. 412, 1–48 (1974).

    CAS  PubMed  Google Scholar 

  58. Nakagawa, Y. & O’Leary, D. D. M. Combinatorial expression patterns of LIM-homeodomain and other regulatory genes parcellate developing thalamus. J. Neurosci. 21, 2711–2725 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Shimamura, K., Hartigan, D. J., Martinez, S., Puelles, L. & Rubenstein, J. L. Longitudinal organization of the anterior neural plate and neural tube. Development 121, 3923–3933 (1995).

    Article  CAS  PubMed  Google Scholar 

  60. Eisenstat, D. D. et al. DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation. J. Comp. Neurol. 414, 217–237 (1999).

    Article  CAS  PubMed  Google Scholar 

  61. Fode, C. et al. A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes Dev. 14, 67–80 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Puelles, L. et al. Pallial and subpallial derivatives in the embryonic chick and mouse telencephalon, traced by the expression of the genes Dlx-2, Emx-1, Nkx-2.1, Pax-6, and Tbr-1. J. Comp. Neurol. 424, 409–438 (2000).

    Article  CAS  PubMed  Google Scholar 

  63. Jones, E. G. & Rubenstein, J. L. R. Expression of regulatory genes during differentiation of thalamic nuclei in mouse and monkey. J. Comp. Neurol. 477, 55–80 (2004).

    Article  CAS  PubMed  Google Scholar 

  64. Jones, E. G. Viewpoint: the core and matrix of thalamic organization. Neuroscience 85, 331–345 (1998).

    Article  CAS  PubMed  Google Scholar 

  65. Muller, E. J. et al. Core and matrix thalamic sub-populations relate to spatio-temporal cortical connectivity gradients. NeuroImage 222, 117224 (2020).

    Article  CAS  PubMed  Google Scholar 

  66. Nagalski, A. et al. Molecular anatomy of the thalamic complex and the underlying transcription factors. Brain Struct. Funct. 221, 2493–2510 (2016).

    Article  CAS  PubMed  Google Scholar 

  67. Stuart, T. & Satija, R. Integrative single-cell analysis. Nat. Rev. Genet. 20, 257–272 (2019).

    Article  CAS  PubMed  Google Scholar 

  68. Saunders, A. et al. Molecular diversity and specializations among the cells of the adult mouse brain. Cell 174, 1015–1030 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Lein, E. S. et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445, 168–176 (2007).

    Article  CAS  PubMed  Google Scholar 

  70. Penzo, M. A. et al. The paraventricular thalamus controls a central amygdala fear circuit. Nature 519, 455–459 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zhu, Y., Wienecke, C. F., Nachtrab, G. & Chen, X. A thalamic input to the nucleus accumbens mediates opiate dependence. Nature 530, 219–222 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Labouebe, G., Boutrel, B., Tarussio, D. & Thorens, B. Glucose-responsive neurons of the paraventricular thalamus control sucrose-seeking behavior. Nat. Neurosci. 19, 999–1002 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Zhu, Y. et al. Dynamic salience processing in paraventricular thalamus gates associative learning. Science 362, 423–429 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ren, S. et al. The paraventricular thalamus is a critical thalamic area for wakefulness. Science 362, 429–434 (2018).

    Article  CAS  PubMed  Google Scholar 

  75. Li, S. & Kirouac, G. J. Projections from the paraventricular nucleus of the thalamus to the forebrain, with special emphasis on the extended amygdala. J. Comp. Neurol. 506, 263–287 (2008).

    Article  PubMed  Google Scholar 

  76. Li, S. & Kirouac, G. J. Sources of inputs to the anterior and posterior aspects of the paraventricular nucleus of the thalamus. Brain Struct. Funct. 217, 257–273 (2012).

    Article  PubMed  Google Scholar 

  77. Dong, X., Li, S. & Kirouac, G. J. Collateralization of projections from the paraventricular nucleus of the thalamus to the nucleus accumbens, bed nucleus of the stria terminalis, and central nucleus of the amygdala. Brain Struct. Funct. 222, 3927–3943 (2017).

    Article  PubMed  Google Scholar 

  78. Matzeu, A., Kerr, T. M., Weiss, F. & Martin-Fardon, R. Orexin-A/hypocretin-1 mediates cocaine-seeking behavior in the posterior paraventricular nucleus of the thalamus via orexin/hypocretin receptor-2. J. Pharmacol. Exp. Ther. 359, 273–279 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Do-Monte, F. H., Minier-Toribio, A., Quinones-Laracuente, K., Medina-Colon, E. M. & Quirk, G. J. Thalamic regulation of sucrose seeking during unexpected reward omission. Neuron 94, 388–400 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Gao, C. et al. Two genetically, anatomically and functionally distinct cell types segregate across anteroposterior axis of paraventricular thalamus. Nat. Neurosci. 23, 217–228 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Pinault, D. & Deschenes, M. Projection and innervation patterns of individual thalamic reticular axons in the thalamus of the adult rat: a three-dimensional, graphic, and morphometric analysis. J. Comp. Neurol. 391, 180–203 (1998).

    Article  CAS  PubMed  Google Scholar 

  82. Lam, Y. W. & Sherman, S. M. Functional organization of the thalamic input to the thalamic reticular nucleus. J. Neurosci. 31, 6791–6799 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Whilden, C. M., Chevee, M., An, S. Y. & Brown, S. P. The synaptic inputs and thalamic projections of two classes of layer 6 corticothalamic neurons in primary somatosensory cortex of the mouse. J. Comp. Neurol. 529, 3751–3771 (2021).

  84. Brunton, J. & Charpak, S. Heterogeneity of cell firing properties and opioid sensitivity in the thalamic reticular nucleus. Neuroscience 78, 303–307 (1997).

    CAS  PubMed  Google Scholar 

  85. Lee, S. H., Govindaiah, G. & Cox, C. L. Heterogeneity of firing properties among rat thalamic reticular nucleus neurons. J. Physiol. 582, 195–208 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Dong, P. et al. A novel cortico-intrathalamic circuit for flight behavior. Nat. Neurosci. 22, 941–949 (2019).

    Article  CAS  PubMed  Google Scholar 

  87. Clemente-Perez, A. et al. Distinct thalamic reticular cell types differentially modulate normal and pathological cortical rhythms. Cell Rep. 19, 2130–2142 (2017).

    Article  CAS  PubMed  Google Scholar 

  88. Martinez-Garcia, R. I. et al. Two dynamically distinct circuits drive inhibition in the sensory thalamus. Nature 583, 813–818 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Brown, H. D., Baker, P. M. & Ragozzino, M. E. The parafascicular thalamic nucleus concomitantly influences behavioral flexibility and dorsomedial striatal acetylcholine output in rats. J. Neurosci. 30, 14390–14398 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Feger, J., Bevan, M. & Crossman, A. R. The projections from the parafascicular thalamic nucleus to the subthalamic nucleus and the striatum arise from separate neuronal populations: a comparison with the corticostriatal and corticosubthalamic efferents in a retrograde fluorescent double-labelling study. Neuroscience 60, 125–132 (1994).

    Article  CAS  PubMed  Google Scholar 

  91. Watson, G. et al. Thalamic projections to the subthalamic nucleus contribute to movement initiation and rescue of parkinsonian symptoms. Sci. Adv. 7, eabe9192 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ye, M., Hayar, A. & Garcia-Rill, E. Cholinergic responses and intrinsic membrane properties of developing thalamic parafascicular neurons. J. Neurophysiol. 102, 774–785 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Beatty, J. A., Sylwestrak, E. L. & Cox, C. L. Two distinct populations of projection neurons in the rat lateral parafascicular thalamic nucleus and their cholinergic responsiveness. Neuroscience 162, 155–173 (2009).

    Article  CAS  PubMed  Google Scholar 

  94. Wang, M. et al. Distinct temporal spike and local field potential activities in the thalamic parafascicular nucleus of parkinsonian rats during rest and limb movement. Neuroscience 330, 57–71 (2016).

    Article  CAS  PubMed  Google Scholar 

  95. Mandelbaum, G. et al. Distinct cortical-thalamic-striatal circuits through the parafascicular nucleus. Neuron 102, 636–652 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Krahe, T. E., El-Danaf, R. N., Dilger, E. K., Henderson, S. C. & Guido, W. Morphologically distinct classes of relay cells exhibit regional preferences in the dorsal lateral geniculate nucleus of the mouse. J. Neurosci. 31, 17437–17448 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kim, I. J., Zhang, Y., Meister, M. & Sanes, J. R. Laminar restriction of retinal ganglion cell dendrites and axons: subtype-specific developmental patterns revealed with transgenic markers. J. Neurosci. 30, 1452–1462 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Rompani, S. B. et al. Different modes of visual integration in the lateral geniculate nucleus revealed by single-cell-initiated transsynaptic tracing. Neuron 93, 767–776 (2017).

    Article  Google Scholar 

  99. Guido, W. Development, form, and function of the mouse visual thalamus. J. Neurophysiol. 120, 211–225 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Grubb, M. S. & Thompson, I. D. Quantitative characterization of visual response properties in the mouse dorsal lateral geniculate nucleus. J. Neurophysiol. 90, 3594–3607 (2003).

    Article  PubMed  Google Scholar 

  101. Marshel, J. H., Kaye, A. P., Nauhaus, I. & Callaway, E. M. Anterior–posterior direction opponency in the superficial mouse lateral geniculate nucleus. Neuron 76, 713–720 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Cruz-Martin, A. et al. A dedicated circuit links direction-selective retinal ganglion cells to the primary visual cortex. Nature 507, 358–361 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Kalish, B. T. et al. Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement. Proc. Natl Acad. Sci. USA 115, E1051–E1060 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Dubin, M. W. & Cleland, B. G. Organization of visual inputs to interneurons of lateral geniculate nucleus of the cat. J. Neurophysiol. 40, 410–427 (1977).

    Article  CAS  PubMed  Google Scholar 

  105. Bickford, M. E., Carden, W. B. & Patel, N. C. Two types of interneurons in the cat visual thalamus are distinguished by morphology, synaptic connections, and nitric oxide synthase content. J. Comp. Neurol. 413, 83–100 (1999).

    Article  CAS  PubMed  Google Scholar 

  106. Pape, H. C. & McCormick, D. A. Electrophysiological and pharmacological properties of interneurons in the cat dorsal lateral geniculate nucleus. Neuroscience 68, 1105–1125 (1995).

    Article  CAS  PubMed  Google Scholar 

  107. Sanchez-Vives, M. V., Bal, T., Kim, U., von Krosigk, M. & McCormick, D. A. Are the interlaminar zones of the ferret dorsal lateral geniculate nucleus actually part of the perigeniculate nucleus? J. Neurosci. 16, 5923–5941 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Leist, M. et al. Two types of interneurons in the mouse lateral geniculate nucleus are characterized by different h-current density. Sci. Rep. 6, 24904 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Giguere, M. & Goldman-Rakic, P. S. Mediodorsal nucleus: areal, laminar, and tangential distribution of afferents and efferents in the frontal lobe of rhesus monkeys. J. Comp. Neurol. 277, 195–213 (1988).

    Article  CAS  PubMed  Google Scholar 

  110. Schmitt, L. I. et al. Thalamic amplification of cortical connectivity sustains attentional control. Nature 545, 219–223 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Rikhye, R. V., Gilra, A. & Halassa, M. M. Thalamic regulation of switching between cortical representations enables cognitive flexibility. Nat. Neurosci. 21, 1753–1763 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Mukherjee, A., Lam, N. H., Wimmer, R. D. & Halassa, M. M. Thalamic circuits for independent control of prefrontal signal and noise. Nature 600, 100–104 (2021).

  113. Wang, J., Hosseini, E., Meirhaeghe, N., Akkad, A. & Jazayeri, M. Reinforcement regulates timing variability in thalamus. eLife 9, e55872 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Groenewegen, H. J. Organization of the afferent connections of the mediodorsal thalamic nucleus in the rat, related to the mediodorsal-prefrontal topography. Neuroscience 24, 379–431 (1988).

    Article  CAS  PubMed  Google Scholar 

  115. Kuramoto, E. et al. Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: a single neuron-tracing study using virus vectors. J. Comp. Neurol. 525, 166–185 (2017).

    Article  PubMed  Google Scholar 

  116. Kuroda, M., Lopez-Mascaraque, L. & Price, J. L. Neuronal and synaptic composition of the mediodorsal thalamic nucleus in the rat: a light and electron microscopic Golgi study. J. Comp. Neurol. 326, 61–81 (1992).

    Article  CAS  PubMed  Google Scholar 

  117. Lavin, A. & Grace, A. A. Dopamine modulates the responsivity of mediodorsal thalamic cells recorded in vitro. J. Neurosci. 18, 10566–10578 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Lu, P. L., Tsai, M. L., Jaw, F. S. & Yen, C. T. Distributions of different types of nociceptive neurons in thalamic mediodorsal nuclei of anesthetized rats. J. Physiol. Sci. 69, 387–397 (2019).

    Article  CAS  PubMed  Google Scholar 

  119. Lyuboslavsky, P., Kizimenko, A. & Brumback, A. C. Two contrasting mediodorsal thalamic circuits target the medial prefrontal cortex. Preprint at bioRxiv https://doi.org/10.1101/2021.01.20.427526 (2021).

  120. Murray, K. D., Choudary, P. V. & Jones, E. G. Nucleus- and cell-specific gene expression in monkey thalamus. Proc. Natl Acad. Sci. USA 104, 1989–1994 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Conley, M., Schmechel, D. E. & Diamond, I. T. Differential distribution of somatostatin-like immunoreactivity in the visual sector of the thalamic reticular nucleus in galago. Eur. J. Neurosci. 3, 237–242 (1991).

    Article  PubMed  Google Scholar 

  122. Dreher, B., Fukada, Y. & Rodieck, R. W. Identification, classification and anatomical segregation of cells with X-like and Y-like properties in the lateral geniculate nucleus of old-world primates. J. Physiol. 258, 433–452 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Usrey, W. M. & Alitto, H. J. Visual functions of the thalamus. Annu. Rev. Vis. Sci. 1, 351–371 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Sadikot, A. F., Parent, A. & Francois, C. Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a PHA-L study of subcortical projections. J. Comp. Neurol. 315, 137–159 (1992).

    Article  CAS  PubMed  Google Scholar 

  125. Russchen, F. T., Amaral, D. G. & Price, J. L. The afferent input to the magnocellular division of the mediodorsal thalamic nucleus in the monkey, Macaca fascicularis. J. Comp. Neurol. 256, 175–210 (1987).

    Article  CAS  PubMed  Google Scholar 

  126. Jager, P. et al. Dual midbrain and forebrain origins of thalamic inhibitory interneurons. eLife 10, e59272 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Krienen, F. M. et al. Innovations present in the primate interneuron repertoire. Nature 586, 262–269 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. O’Leary, T. P. et al. Extensive and spatially variable within-cell-type heterogeneity across the basolateral amygdala. eLife 9, e59003 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Fulcher, B. D., Murray, J. D., Zerbi, V. & Wang, X. J. Multimodal gradients across mouse cortex. Proc. Natl Acad. Sci. USA 116, 4689–4695 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Braak, H. & Braak, E. Alzheimer’s disease affects limbic nuclei of the thalamus. Acta Neuropathol. 81, 261–268 (1991).

    Article  CAS  PubMed  Google Scholar 

  131. Popken, G. J., Bunney, W. E. Jr, Potkin, S. G. & Jones, E. G. Subnucleus-specific loss of neurons in medial thalamus of schizophrenics. Proc. Natl Acad. Sci. USA 97, 9276–9280 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Henderson, J. M., Carpenter, K., Cartwright, H. & Halliday, G. M. Loss of thalamic intralaminar nuclei in progressive supranuclear palsy and Parkinson’s disease: clinical and therapeutic implications. Brain 123, 1410–1421 (2000).

    Article  PubMed  Google Scholar 

  133. Woodward, N. D., Giraldo-Chica, M., Rogers, B. & Cascio, C. J. Thalamocortical dysconnectivity in autism spectrum disorder: an analysis of the Autism Brain Imaging Data Exchange. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 2, 76–84 (2017).

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The Warren Alpert Distinguished Scholar Award supported D.S.R. The J. Douglas Tan Postdoctoral Fellowship supported Y.Z. This work was supported by the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, the Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, the James and Patricia Poitras Center for Psychiatric Disorders Research at MIT, the NIH–NINDS (R01NS113245) and the NIH BRAIN Initiative (U01MH114819, to G.F.).

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  1. These authors contributed equally: Dheeraj S. Roy, Ying Zhang.

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  1. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Dheeraj S. Roy & Guoping Feng

  2. Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, MIT, Cambridge, MA, USA

    Ying Zhang, Michael M. Halassa & Guoping Feng

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Roy, D.S., Zhang, Y., Halassa, M.M. et al. Thalamic subnetworks as units of function. Nat Neurosci 25, 140–153 (2022). https://doi.org/10.1038/s41593-021-00996-1

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