Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Interneuron cell types are fit to function

Abstract

Understanding brain circuits begins with an appreciation of their component parts — the cells. Although GABAergic interneurons are a minority population within the brain, they are crucial for the control of inhibition. Determining the diversity of these interneurons has been a central goal of neurobiologists, but this amazing cell type has so far defied a generalized classification system. Interneuron complexity within the telencephalon could be simplified by viewing them as elaborations of a much more finite group of developmentally specified cardinal classes that become further specialized as they mature. Our perspective emphasizes that the ultimate goal is to dispense with classification criteria and directly define interneuron types by function.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Multiple dimensions of interneuron diversity.
Figure 2: Interneuron subtypes are generated from discrete proliferative regions within the subpallium.
Figure 3: Two faces of interneuron function.
Figure 4: Coordination and flow control hypotheses of recruitment.

References

  1. Ascoli, G. A. et al. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nature Rev. Neurosci. 9, 557–568 (2008). This is the best effort to date by physiologists, anatomists and developmental neurobiologists to come to a common nomenclature for GABAergic interneurons.

    CAS  Google Scholar 

  2. Freund, T. F. & Buzsáki, G. Interneurons of the hippocampus. Hippocampus 6, 347–470 (1996).

    CAS  PubMed  Google Scholar 

  3. Markram, H. et al. Interneurons of the neocortical inhibitory system. Nature Rev. Neurosci. 5, 793–807 (2004).

    CAS  Google Scholar 

  4. Parra, P., Gulyás, A. I. & Miles, R. How many subtypes of inhibitory cells in the hippocampus? Neuron 20, 983–993 (1998).

    CAS  PubMed  Google Scholar 

  5. Brody, T. & Odenwald, W. F. Regulation of temporal identities during Drosophila neuroblast lineage development. Curr. Opin. Cell Biol. 17, 672–675 (2005).

    CAS  PubMed  Google Scholar 

  6. Xu, Q., Cobos, I., De La Cruz, E., Rubenstein, J. L. & Anderson, S. A. Origins of cortical interneuron subtypes. J. Neurosci. 24, 2612–2622 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Leone, D. P., Srinivasan, K., Chen, B., Alcamo, E. & McConnell, S. K. The determination of projection neuron identity in the developing cerebral cortex. Curr. Opin. Neurobiol. 18, 28–35 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Gelman, D., Griveau, A. & Dehorter, N. A wide diversity of cortical GABAergic interneurons derives from the embryonic preoptic area. J. Neurosci. 31, 16570–16580 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. O'Leary, D. D. M. & Borngasser, D. Cortical ventricular zone progenitors and their progeny maintain spatial relationships and radial patterning during preplate development indicating an early protomap. Cereb. Cortex 16, i46–i56 (2006).

    PubMed  Google Scholar 

  10. Anderson, S. A., Eisenstat, D. D., Shi, L. & Rubenstein, J. L. Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278, 474–476 (1997). This paper demonstrates that cortical interneurons are derived subpallially.

    ADS  CAS  PubMed  Google Scholar 

  11. Wichterle, H., Turnbull, D. H., Nery, S., Fishell, G. & Alvarez-Buylla, A. In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain. Development 128, 3759–3771 (2001). This paper provided in vivo evidence that specific interneurons are derived from specific embryonic progenitor zones.

    CAS  PubMed  Google Scholar 

  12. Nery, S., Fishell, G. & Corbin, J. G. The caudal ganglionic eminence is a source of distinct cortical and subcortical cell populations. Nature Neurosci. 5, 1279–1287 (2002).

    CAS  PubMed  Google Scholar 

  13. Butt, S. J. et al. The temporal and spatial origins of cortical interneurons predict their physiological subtype. Neuron 48, 591–604 (2005).

    CAS  PubMed  Google Scholar 

  14. Lee, S., Hjerling-Leffler, J., Zagha, E., Fishell, G. & Rudy, B. The largest group of superficial neocortical GABAergic interneurons expresses ionotropic serotonin receptors. J. Neurosci. 30, 16796–16808 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Miyoshi, G. et al. Genetic fate mapping reveals that the caudal ganglionic eminence produces a large and diverse population of superficial cortical interneurons. J. Neurosci. 30, 1582–1594 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Fogarty, M. et al. Spatial genetic patterning of the embryonic neuroepithelium generates GABAergic interneuron diversity in the adult cortex. J. Neurosci. 27, 10935–10946 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Du, T., Xu, Q., Ocbina, P. J. & Anderson, S. A. NKX2.1 specifies cortical interneuron fate by activating Lhx6. Development 135, 1559–1567 (2008).

    CAS  PubMed  Google Scholar 

  18. Tricoire, L. et al. Common origins of hippocampal Ivy and nitric oxide synthase expressing neurogliaform cells. J. Neurosci. 30, 2165–2176 (2010). This paper compared references 11–15 to demonstrate that similar interneuron subtypes in the cortex versus the hippocampus could be derived from distinct progenitor zones.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Armstrong, C. & Soltesz, I. Basket cell dichotomy in microcircuit function. J. Physiol. 590, 683–694 (2012).

    CAS  PubMed  Google Scholar 

  20. McBain, C. J. & Fisahn, A. E. Interneurons unbound. Nature Rev. Neurosci. 2, 11–23 (2001).

    CAS  Google Scholar 

  21. Chittajallu, R. et al. Dual origins of functionally distinct O-LM interneurons revealed by differential 5–HT3AR expression. Nature Neurosci. 16, 1598–1607 (2013).

    CAS  PubMed  Google Scholar 

  22. Marín, O., Anderson, S. A. & Rubenstein, J. L. R. Origin and molecular specification of striatal interneurons. J. Neurosci. 20, 6063–6076 (2000). This paper reports our best understanding so far of the origins of striatal interneurons.

    PubMed  PubMed Central  Google Scholar 

  23. Wang, B., Waclaw, R. R., Allen, Z. J., Guillemot, F. & Campbell, K. Ascl1 is a required downstream effector of Gsx gene function in the embryonic mouse telencephalon. Neural Dev. 4, 5 (2009).

    PubMed  PubMed Central  Google Scholar 

  24. Wang, B. et al. Loss of Gsx1 and Gsx2 function rescues distinct phenotypes in Dlx1/2 mutants. J. Comp. Neurol. 521, 1561–1584 (2013).

    CAS  PubMed  Google Scholar 

  25. Long, J. E., Cobos, I., Potter, G. B. & Rubenstein, J. L. Dlx1&2 and Mash1 transcription factors control MGE and CGE patterning and differentiation through parallel and overlapping pathways. Cereb. Cortex 19 (Suppl. 1), i96–i106 (2009).

    PubMed  PubMed Central  Google Scholar 

  26. Schuurmans, C. & Guillemot, F. Molecular mechanisms underlying cell fate specification in the developing telencephalon. Curr. Opin. Neurobiol. 12, 26–34 (2002).

    CAS  PubMed  Google Scholar 

  27. Stühmer, T., Anderson, S. A., Ekker, M. & Rubenstein, J. L. R. Ectopic expression of the Dlx genes induces glutamic acid decarboxylase and Dlx expression. Development 129, 245–252 (2002).

    PubMed  Google Scholar 

  28. Cobos, I., Borello, U. & Rubenstein, J. L. Dlx transcription factors promote migration through repression of axon and dendrite growth. Neuron 54, 873–888 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Cobos, I. et al. Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Nature Neurosci. 8, 1059–1068 (2005).

    CAS  PubMed  Google Scholar 

  30. Colombo, E. et al. Inactivation of Arx, the murine ortholog of the X-linked lissencephaly with ambiguous genitalia gene, leads to severe disorganization of the ventral telencephalon with impaired neuronal migration and differentiation. J. Neurosci. 27, 4786–4798 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Bassett, E. A. & Wallace, V. A. Cell fate determination in the vertebrate retina. Trends Neurosci. 35, 565–573 (2012).

    CAS  PubMed  Google Scholar 

  32. Leber, S. M., Breedlove, S. M. & Sanes, J. R. Lineage, arrangement, and death of clonally related motoneurons in chick spinal cord. J. Neurosci. 10, 2451–2462 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Walsh, C. & Cepko, C. L. Clonally related cortical cells show several migration patterns. Science 241, 1342–1345 (1988).

    ADS  CAS  PubMed  Google Scholar 

  34. Sussel, L., Marín, O., Kimura, S. & Rubenstein, J. L. Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. Development 126, 3359–3370 (1999).

    CAS  PubMed  Google Scholar 

  35. Butt, S. J. et al. The requirement of Nkx2–1 in the temporal specification of cortical interneuron subtypes. Neuron 59, 722–732 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Taniguchi, H., Lu, J. & Huang, Z. J. The spatial and temporal origin of chandelier cells in mouse neocortex. Science 339, 70–74 (2013). References 35 and 36 provide support for Nkx2-1 functioning as a master regulator of the fate of specific cortical interneuron identities.

    ADS  CAS  PubMed  Google Scholar 

  37. Inan, M., Welagen, J. & Anderson, S. A. Spatial and temporal bias in the mitotic origins of somatostatin- and parvalbumin-expressing interneuron subgroups and the chandelier subtype in the medial ganglionic eminence. Cereb. Cortex 22, 820–827 (2012).

    PubMed  Google Scholar 

  38. Denaxa, M. et al. Maturation-promoting activity of SATB1 in MGE-derived cortical interneurons. Cell Rep. 2, 1351–1362 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Close, J. et al. Satb1 is an activity-modulated transcription factor required for the terminal differentiation and connectivity of medial ganglionic eminence-derived cortical interneurons. J. Neurosci. 32, 17690–17705 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Flames, N. et al. Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes. J. Neurosci. 27, 9682–9695 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Ciceri, G. et al. Lineage-specific laminar organization of cortical GABAergic interneurons. Nature Neurosci. 16, 1199–1210 (2013).

    CAS  PubMed  Google Scholar 

  42. Brown, K. N. et al. Clonal production and organization of inhibitory interneurons in the neocortex. Science 334, 480–486 (2011).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  43. Corbin, J. G., Nery, S. & Fishell, G. Telencephalic cells take a tangent: non-radial migration in the mammalian forebrain. Nature Neurosci. 4, 1177–1182 (2001).

    CAS  PubMed  Google Scholar 

  44. Marín, O. & Rubenstein, J. L. R. A long, remarkable journey: tangential migration in the telencephalon. Nature Rev. Neurosci. 2, 780–790 (2001).

    Google Scholar 

  45. Hobert, O. Specification of the nervous system. In Wormbook: the Online Review of C. elegans Biology http://www.wormbook.org/ (2005).

    Google Scholar 

  46. Beier, K. T., Samson, M. E., Matsuda, T. & Cepko, C. L. Conditional expression of the TVA receptor allows clonal analysis of descendents from Cre-expressing progenitor cells. Dev. Biol. 353, 309–320 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Cancedda, L., Fiumelli, H., Chen, K. & Poo, M. M. Excitatory GABA action is essential for morphological maturation of cortical neurons in vivo. J. Neurosci. 27, 5224–5235 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Bortone, D. & Polleux, F. KCC2 expression promotes the termination of cortical interneuron migration in a voltage-sensitive calcium-dependent manner. Neuron 62, 53–71 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. De Marco García, N. V., Karayannis, T. & Fishell, G. Neuronal activity is required for the development of specific cortical interneuron subtypes. Nature 472, 351–355 (2011). References 48 and 49 provide the best evidence so far for a role for activity in the positioning and maturation of cortical interneurons.

    ADS  PubMed  PubMed Central  Google Scholar 

  50. McKinsey, G. L., Lindtner, S., Trzcinski, B. & Visel, A. Dlx1&2-dependent expression of Zfhx1b (Sip1, Zeb2) regulates the fate switch between cortical and striatal interneurons. Neuron 77, 83–98 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. van den Berghe, V. et al. Directed migration of cortical interneurons depends on the cell-qutonomous action of Sip1. Neuron 77, 70–82 (2013).

    CAS  PubMed  Google Scholar 

  52. Lyons, M. R., Schwarz, C. M. & West, A. E. Members of the myocyte enhancer factor 2 transcription factor family differentially regulate Bdnf transcription in response to neuronal depolarization. J. Neurosci. 32, 12780–12785 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. West, A. E. & Greenberg, M. E. Neuronal activity-regulated gene transcription in synapse development and cognitive function. Cold Spring Harb. Perspect. Biol. 3, a005744 (2011).

    PubMed  PubMed Central  Google Scholar 

  54. Southwell, D. G., Froemke, R. C., Alvarez-Buylla, A., Stryker, M. P. & Gandhi, S. P. Cortical plasticity induced by inhibitory neuron transplantation. Science 327, 1145–1148 (2010).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bráz, J. M. et al. Forebrain GABAergic neuron precursors integrate into adult spinal cord and reduce injury-induced neuropathic pain. Neuron 74, 663–675 (2012).

    PubMed  PubMed Central  Google Scholar 

  56. Martínez-Cerdeño, V. et al. Embryonic MGE precursor cells grafted into adult rat striatum integrate and ameliorate motor symptoms in 6-OHDA-lesioned rats. Cell Stem Cell 6, 238–250 (2010).

    PubMed  PubMed Central  Google Scholar 

  57. Taniguchi, H. et al. A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71, 995–1013 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Hippenmeyer, S. et al. A developmental switch in the response of DRG neurons to ETS transcription factor signaling. PLoS Biol. 3, e159 (2005).

    PubMed  PubMed Central  Google Scholar 

  59. Douglas, R. J. & Martin, K. A. A functional microcircuit for cat visual cortex. J. Physiol. 440, 735–69 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Douglas, R. J., Koch, C., Mahowald, M. & Martin, K. A. Recurrent excitation in neocortical circuits. Science 269, 981–985 (1995).

    ADS  CAS  PubMed  Google Scholar 

  61. Buzsáki, G. & Draguhn, A. Neuronal oscillations in cortical networks. Science 304, 1926–1929 (2004).

    ADS  PubMed  Google Scholar 

  62. Wang X. J., Tegnér, J., Constantinidis, C., Goldman-Rakic, P. S. Division of labor among distinct subtypes of inhibitory neurons in a cortical microcircuit of working memory. Proc. Natl Acad. Sci. USA. 101, 1368–1373 (2004).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  63. Silver, R. A. Neuronal arithmetic. Nature Rev. Neurosci. 11, 474–489 (2010).

    CAS  Google Scholar 

  64. Holt, G. R. & Koch, C. Shunting inhibition does not have a divisive effect on firing rates. Neural Comput. 9, 1001–1013 (1997).

    CAS  PubMed  Google Scholar 

  65. Carandini, M. & Heeger, D. J. Normalization as a canonical neural computation. Nature Rev. Neurosci. 13, 51–62 (2012).

    CAS  Google Scholar 

  66. Schwartz, O. & Simoncelli, E. P. Natural signal statistics and sensory gain control. Nature Neurosci. 4, 819–825 (2001).

    CAS  PubMed  Google Scholar 

  67. Mitchell, S. J. & Silver, R. A. Shunting inhibition modulates neuronal gain during synaptic excitation. Neuron 38, 433–445 (2003).

    CAS  PubMed  Google Scholar 

  68. Tiesinga, P. H. & Sejnowski, T. J. Rapid temporal modulation of synchrony by competition in cortical interneuron networks. Neural Comput. 16, 251–275 (2004).

    CAS  PubMed  PubMed Central  MATH  Google Scholar 

  69. Chance, F. S., Abbott, L. F. & Reyes, A. D. Gain modulation from background synaptic input. Neuron 35, 773–782 (2002).

    CAS  PubMed  Google Scholar 

  70. Taniguchi, H., Huang, Z. J. & Callaway, E. M. Contrast dependence and differential contributions from somatostatin- and parvalbumin-expressing neurons to spatial integration in mouse V1. J. Neurosci. 33, 11145–11154 (2013).

    PubMed  PubMed Central  Google Scholar 

  71. van Vreeswijk, C. & Sompolinsky, H. Chaos in neuronal networks with balanced excitatory and inhibitory activity. Science 274, 1724–1726 (1996).

    ADS  CAS  PubMed  Google Scholar 

  72. Wehr, M. & Zador, A. M. Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature 426, 442–446 (2003).

    ADS  CAS  PubMed  Google Scholar 

  73. Haider, B., Duque, A. & Hasenstaub, A. R. Neocortical network activity in vivo is generated through a dynamic balance of excitation and inhibition. J. Neurosci. 26, 4535–4545 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Okun, M. & Lampl, I. Instantaneous correlation of excitation and inhibition during ongoing and sensory-evoked activities. Nature Neurosci. 11, 535–537 (2008).

    CAS  PubMed  Google Scholar 

  75. Haider, B., Häusser, M. & Carandini, M. Inhibition dominates sensory responses in the awake cortex. Nature 493, 97–100 (2013). This study demonstrates that during wakefulness inhibition strongly shapes the spatial and temporal response properties of visual cortical neurons.

    ADS  PubMed  Google Scholar 

  76. Pouille, F. & Scanziani, M. Enforcement of temporal fidelity in pyramidal cells by somatic feed-forward inhibition. Science 293, 1159–1163 (2001).

    CAS  PubMed  Google Scholar 

  77. Renart, A. et al. The asynchronous state in cortical circuits. Science 327, 587–590 (2010).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  78. Rudy, B., Fishell, G., Lee, S. & Hjerling-Leffler, J. Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons. Dev. Neurobiol. 71, 45–61 (2011).

    PubMed  PubMed Central  Google Scholar 

  79. Xu, X., Roby, K. D. & Callaway, E. M. Immunochemical characterization of inhibitory mouse cortical neurons: three chemically distinct classes of inhibitory cells. J. Comp. Neurol. 518, 389–340 (2010).

    PubMed  PubMed Central  Google Scholar 

  80. Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neurosci. 8, 1263–1268 (2005).

    CAS  PubMed  Google Scholar 

  81. Zhang, F., Aravanis, A. M., Adamantidis, A., de Lecea, L. & Deisseroth, K. Circuit-breakers: optical technologies for probing neural signals and systems. Nature Rev. Neurosci. 8, 577–581 (2007).

    CAS  Google Scholar 

  82. Somogyi, P., Tamas, G., Lujan, R. & Buhl, E. H. Salient features of synaptic organisation in the cerebral cortex. Brain Res. Rev. 26, 113–135 (1998).

    CAS  PubMed  Google Scholar 

  83. Galarreta, M. & Hestrin, S. A network of fast-spiking cells in the neocortex connected by electrical synapses. Nature 402, 72–75 (1999).

    ADS  CAS  PubMed  Google Scholar 

  84. Kvitsiani, D., Ranade, S., Hangya, B., Taniguchi, H., Huang, J. Z. & Kepecs, A. Distinct behavioural and network correlates of two interneuron types in prefrontal cortex. Nature 498, 363–366 (2013). This study provides evidence that genetically identified interneuron classes are recruited at specific behavioural events.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  85. Pfeffer, C. K., Xue, M., He, M., Huang, Z. J. & Scanziani, M. Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons. Nature Neurosci. 16, 1068–1076 (2013). This paper defines the rules of connectivity for marker-defined interneuron classes.

    CAS  PubMed  Google Scholar 

  86. Szabadics, J., Lorincz, A. & Tamás, G. Beta and gamma frequency synchronization by dendritic gabaergic synapses and gap junctions in a network of cortical interneurons. J. Neurosci. 21, 5824–5831 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Royer, S. et al. Control of timing, rate and bursts of hippocampal place cells by dendritic and somatic inhibition. Nature Neurosci. 15, 769–775 (2012). The first direct demonstration of the distinct roles of PV and SST interneurons in awake hippocampus.

    CAS  PubMed  Google Scholar 

  88. Lovett-Barron, M. et al. Regulation of neuronal input transformations by tunable dendritic inhibition. Nature Neurosci. 15, 423–430 (2012).

    CAS  PubMed  Google Scholar 

  89. Losonczy, A., Zemelman, B. V., Vaziri, A. & Magee, J. C. Network mechanisms of theta related neuronal activity in hippocampal CA1 pyramidal neurons. Nature Neurosci. 13, 967–972 (2010).

    CAS  PubMed  Google Scholar 

  90. Wilson, N. R., Runyan, C. A., Wang, F. L. & Sur, M. Division and subtraction by distinct cortical inhibitory networks in vivo. Nature 488, 343–348 (2012).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  91. Atallah, B. V., Bruns, W., Carandini, M. & Scanziani, M. Parvalbumin-expressing interneurons linearly transform cortical responses to visual stimuli. Neuron 73, 159–170 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Lee, S.-H. et al. Activation of specific interneurons improves V1 feature selectivity and visual perception. Nature 488, 379–383 (2012).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  93. Murayama, M., Pérez-Garci, E., Nevian, T., Bock, T., Senn, W & Larkum, M. E. Dendritic encoding of sensory stimuli controlled by deep cortical interneurons. Nature 457, 1137–1141 (2009). This study reveals how a specific interneuron type gates bursting in layer 5 pyramidal cells.

    ADS  CAS  PubMed  Google Scholar 

  94. Berger, T. K., Perin, R., Silberberg, G. & Markram, H. Frequency-dependent disynaptic inhibition in the pyramidal network: a ubiquitous pathway in the developing rat neocortex. J. Physiol. 587, 5411–5425 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Kapfer, C., Glickfeld, L. L., Atallah, B. V. & Scanziani, M. Supralinear increase of recurrent inhibition during sparse activity in the somatosensory cortex. Nature Neurosci. 10, 743–753 (2007).

    CAS  PubMed  Google Scholar 

  96. Miles, R., Tóth, K., Gulyas, A. I., Hájos, N. & Freund, T. F. Differences between somatic and dendritic inhibition in the hippocampus. Neuron 16, 815–823 (1996).

    CAS  PubMed  Google Scholar 

  97. Adesnik, H. & Scanziani, M. Lateral competition for cortical space by layer-specific horizontal circuits. Nature 464, 1155–1160 (2010).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  98. Xu, H., Jeong, H. Y., Tremblay, R. & Rudy, B. Neocortical somatostatin-expressing GABAergic interneurons disinhibit the thalamorecipient layer 4. Neuron 77, 155–167 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Hájos, N., Acsády, L. & Freund, T. F. Target selectivity and neurochemical characteristics of VIP-immunoreactive interneurons in the rat dentate gyrus. Eur. J. Neurosci. 8, 1415–1431 (1996).

    PubMed  Google Scholar 

  100. Acsády, L., Görcs, T. J. & Freund, T. F. Different populations of vasoactive intestinal polypeptide-immunoreactive interneurons are specialized to control pyramidal cells or interneurons in the hippocampus. Neuroscience 73, 317–334 (1996).

    PubMed  Google Scholar 

  101. Lee, S., Kruglikov, I., Huang, Z. J., Fishell, G. & Rudy, B. A disinhibitory circuit mediates motor integration in the somatosensory cortex. Nature Neurosci. 16, 1662–1670 (2013).

    CAS  PubMed  Google Scholar 

  102. Pi, H.-J., Hangya, B., Kvitsiani, D., Sanders, J. I., Huang, Z. J. & Kepecs, A. Cortical interneurons that specialize in disinhibitory control. Nature 503, 521–524 (2013). This study is a direct demonstration that VIP-expressing interneurons are disinhibitory and are recruited by behavioural reinforcers, which together with references 85 and 101 reveals that this function is supported by a microcircuit conserved across regions.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  103. Hestrin, S. & Armstrong, W. E. Morphology and physiology of cortical neurons in layer I. J. Neurosci. 16, 5290–5300 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Jiang, X., Wang, G., Lee, A. J., Stornetta, R. L. & Zhu, J. J. The organization of two new cortical interneuronal circuits. Nature Neurosci. 16, 210–218 (2013).

    CAS  PubMed  Google Scholar 

  105. Letzkus, J. J. et al. A disinhibitory microcircuit for associative fear learning in the auditory cortex. Nature 480, 331–335 (2011). This paper demonstrates a functionally relevant disinhibitory circuit in the auditory cortex.

    ADS  CAS  PubMed  Google Scholar 

  106. Lapray, D. et al. Behavior-dependent specialization of identified hippocampal interneurons. Nature Neurosci. 15, 1265–1271 (2012).

    CAS  PubMed  Google Scholar 

  107. Varga, C., Golshani, P. & Soltesz, I. Frequency-invariant temporal ordering of interneuronal discharges during hippocampal oscillations in awake mice. Proc. Natl Acad. Sci. USA 109, E2726–E2734 (2012). This article demonstrates the hippocampal recruitment of distinct interneuron types in awake mice.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  108. Gentet, L. J. et al. Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex. Nature Neurosci. 15, 607–612 (2012).

    CAS  PubMed  Google Scholar 

  109. Gentet, L. J., Avermann, M., Matyas, F., Staiger, J. F. & Petersen, C. C. H. Membrane potential dynamics of GABAergic neurons in the barrel cortex of behaving mice. Neuron 65, 422–435 (2010).

    CAS  PubMed  Google Scholar 

  110. Csicsvari, J., Hirase, H., Czurko, A. & Buzsáki, G. Reliability and state dependence of pyramidal cell-interneuron synapses in the hippocampus: an ensemble approach in the behaving rat. Neuron 21, 179–189 (1998).

    CAS  PubMed  Google Scholar 

  111. Whittington, M. A. & Traub, R. D. Interneuron diversity series: inhibitory interneurons and network oscillations in vitro. Trends Neurosci. 26, 676–682 (2003).

    CAS  PubMed  Google Scholar 

  112. Buzsáki, G. & Chrobak, J. J. Temporal structure in spatially organized neuronal ensembles: a role for interneuronal networks. Curr. Opin. Neurobiol. 5, 504–510 (1995).

    PubMed  Google Scholar 

  113. Klausberger, T., et al. Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo. Nature 421, 844–848 (2003). An elegant demonstration of how different interneuron types specialize in specific network oscillations.

    ADS  CAS  PubMed  Google Scholar 

  114. Klausberger, T., Márton, L. F., Baude, A., Roberts, J., Magill, J. S. & Somogyi, P. Spike timing of dendrite-targeting bistratified cells during hippocampal network oscillations in vivo. Nature Neurosci. 7, 41–47 (2004).

    CAS  PubMed  Google Scholar 

  115. Klausberger, T. et al. Complementary roles of cholecystokinin- and parvalbumin-expressing GABAergic neurons in hippocampal network oscillations. J. Neurosci. 25, 9782–9793 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Tukker, J. J., Fuentealba, P., Hartwich, K., Somogyi, P. & Klausberger, T. Cell type-specific tuning of hippocampal interneuron firing during gamma oscillations in vivo. J. Neurosci. 27, 8184–8189 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Klausberger, T. & Somogyi, P. Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 321, 53–57 (2008).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  118. Cardin, J. A., et al. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459, 663–667 (2009).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  119. Sohal, V. S., Zhang, F., Yizhar, O. & Deisseroth, K. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459, 698–702 (2009). References 118 and 119 provided the first causal evidence for the role of PV interneurons in gamma oscillations.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  120. Mountcastle, V. B., Talbot, W. H., Sakata, H., & Hyvarinen, J. Cortical neuronal mechanisms in flutter-vibration studied in unanesthetized monkeys: neuronal periodicity and frequency discrimination. J. Neurophysiol. 32, 452–484 (1969).

    CAS  PubMed  Google Scholar 

  121. Mitchell, J. F., Sundberg, K. A. & Reynolds, J. H. Differential attention-dependent response modulation across cell classes in macaque visual area V4. Neuron 55, 131–141 (2007).

    CAS  PubMed  Google Scholar 

  122. Isomura, Y., Harukuni, R., Takekawa, T., Aizawa, H. & Fukai, T. Microcircuitry coordination of cortical motor information in self-initiation of voluntary movements. Nature Neurosci. 12, 1586–1593 (2009).

    CAS  PubMed  Google Scholar 

  123. Hayden, B. Y., Pearson, J. M. & Platt, M. L. Neuronal basis of sequential foraging decisions in a patchy environment. Nature Neurosci. 14, 933–939 (2011).

    CAS  PubMed  Google Scholar 

  124. Carandini, M. From circuits to behavior: a bridge too far? Nature Neurosci. 15, 507–509 (2012).

    CAS  PubMed  Google Scholar 

  125. Alitto, H. J. & Dan, Y. Cell-type-specific modulation of neocortical activity by basal forebrain input. Front. Syst. Neurosci. 6, 79 (2013).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Work in the authors' laboratories is supported by grants from the US National Institutes of Health (R01NS075531 to A.K. and MH071679, MH095147, NS074972 and NS081297 to G.F.) and generous support from the McKnight (A.K.) and Simons Foundations (G.F.). We are grateful to G. Buzsaki, C. McBain, B. Rudy, M. Long, R. Tsien and members of our laboratories for discussions and comments. We thank J. Demidschstein for creating Fig. 2. and J. Kuhl for Figs 1 and 3.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Adam Kepecs or Gordon Fishell.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Reprints and permissions information is available at www.nature.com/reprints.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kepecs, A., Fishell, G. Interneuron cell types are fit to function. Nature 505, 318–326 (2014). https://doi.org/10.1038/nature12983

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature12983

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing