Abstract
Synchronized oscillations and inhibitory interneurons have important and interconnected roles within cortical microcircuits. In particular, interneurons defined by the fast-spiking phenotype and expression of the calcium-binding protein parvalbumin1,2 have been suggested to be involved in gamma (30â80âHz) oscillations3,4,5,6,7, which are hypothesized to enhance information processing8,9. However, because parvalbumin interneurons cannot be selectively controlled, definitive tests of their functional significance in gamma oscillations, and quantitative assessment of the impact of parvalbumin interneurons and gamma oscillations on cortical circuits, have been lacking despite potentially enormous significance (for example, abnormalities in parvalbumin interneurons may underlie altered gamma-frequency synchronization and cognition in schizophrenia10 and autism11). Here we use a panel of optogenetic technologies12,13,14 in mice to selectively modulate multiple distinct circuit elements in neocortex, alone or in combination. We find that inhibiting parvalbumin interneurons suppresses gamma oscillations in vivo, whereas driving these interneurons (even by means of non-rhythmic principal cell activity) is sufficient to generate emergent gamma-frequency rhythmicity. Moreover, gamma-frequency modulation of excitatory input in turn was found to enhance signal transmission in neocortex by reducing circuit noise and amplifying circuit signals, including inputs to parvalbumin interneurons. As demonstrated here, optogenetics opens the door to a new kind of informational analysis of brain function, permitting quantitative delineation of the functional significance of individual elements in the emergent operation and function of intact neural circuitry.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kawaguchi, Y. & Kubota, Y. Neurochemical features and synaptic connections of large physiologically-identified GABAergic cells in the rat frontal cortex. Neuroscience 85, 677â701 (1998)
Toledo-Rodriguez, M. et al. Correlation maps allow neuronal electrical properties to be predicted from single-cell gene expression profiles in rat neocortex. Cereb. Cortex 14, 1310â1327 (2004)
Freund, T. F. Interneuron diversity series: Rhythm and mood in perisomatic inhibition. Trends Neurosci. 26, 489â495 (2003)
Whittington, M. A., Traub, R. D. & Jefferys, J. G. Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation. Nature 373, 612â615 (1995)
Ylinen, A. et al. Intracellular correlates of hippocampal theta rhythm in identified pyramidal cells, granule cells, and basket cells. Hippocampus 5, 78â90 (1995)
Tamas, G., Buhl, E. H., Lorincz, A. & Somogyi, P. Proximally targeted GABAergic synapses and gap junctions synchronize cortical interneurons. Nature Neurosci. 3, 366â371 (2000)
Fuchs, E. C. et al. Recruitment of parvalbumin-positive interneurons determines hippocampal function and associated behavior. Neuron 53, 591â604 (2007)
Konig, P., Engel, A. K. & Singer, W. Integrator or coincidence detector? The role of the cortical neuron revisited. Trends Neurosci. 19, 130â137 (1996)
Womelsdorf, T. et al. Modulation of neuronal interactions through neuronal synchronization. Science 316, 1609â1612 (2007)
Lewis, D. A., Hashimoto, T. & Volk, D. W. Cortical inhibitory neurons and schizophrenia. Nature Rev. Neurosci. 6, 312â324 (2005)
Orekhova, E. V. et al. Excess of high frequency electroencephalogram oscillations in boys with autism. Biol. Psychiatry 62, 1022â1029 (2007)
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neurosci. 8, 1263â1268 (2005)
Zhang, F. et al. Multimodal fast optical interrogation of neural circuitry. Nature 446, 633â639 (2007)
Aravanis, A. M. et al. An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J. Neural Eng. 4, S143âS156 (2007)
Meyer, A. H., Katona, I., Blatow, M., Rozov, A. & Monyer, H. In vivo labeling of parvalbumin-positive interneurons and analysis of electrical coupling in identified neurons. J. Neurosci. 22, 7055â7064 (2002)
Livet, J. et al. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 450, 56â62 (2007)
Conde, F., Lund, J. S. & Lewis, D. A. The hierarchical development of monkey visual cortical regions as revealed by the maturation of parvalbumin-immunoreactive neurons. Brain Res. 96, 261â276 (1996)
Raghavachari, S. et al. Gating of human theta oscillations by a working memory task. J. Neurosci. 21, 3175â3183 (2001)
Howard, M. W. et al. Gamma oscillations correlate with working memory load in humans. Cereb. Cortex 13, 1369â1374 (2003)
de Ruyter van Steveninck, R. R., Lewen, G. D., Strong, S. P., Koberle, R. & Bialek, W. Reproducibility and variability in neural spike trains. Science 275, 1805â1808 (1997)
Arenkiel, B. R. et al. In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2. Neuron 54, 205â218 (2007)
Wang, H. et al. High-speed mapping of synaptic connectivity using photostimulation in Channelrhodopsin-2 transgenic mice. Proc. Natl Acad. Sci. USA 104, 8143â8148 (2007)
Gradinaru, V. et al. Targeting and readout strategies for fast optical neural control in vitro and in vivo . J. Neurosci. 27, 14231 (2007)
Bannister, A. P. Inter- and intra-laminar connections of pyramidal cells in the neocortex. Neurosci. Res. 53, 95â103 (2005)
Sanchez-Vives, M. V. & McCormick, D. A. Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nature Neurosci. 3, 1027â1034 (2000)
Luczak, A., Bartho, P., Marguet, S. L., Buzsaki, G. & Harris, K. D. Sequential structure of neocortical spontaneous activity in vivo . Proc. Natl Acad. Sci. USA 104, 347â352 (2007)
Baccus, S. A. & Meister, M. Fast and slow contrast adaptation in retinal circuitry. Neuron 36, 909â919 (2002)
Szabadics, J. et al. Excitatory effect of GABAergic axo-axonic cells in cortical microcircuits. Science 311, 233â235 (2006)
Fries, P., Reynolds, J. H., Rorie, A. E. & Desimone, R. Modulation of oscillatory neuronal synchronization by selective visual attention. Science 291, 1560â1563 (2001)
Rodriguez, E. et al. Perception's shadow: long-distance synchronization of human brain activity. Nature 397, 430â433 (1999)
Acknowledgements
We thank S. Arber for her gift of the PV::Cre mice, and we acknowledge the advice and suggestions of R. C. Malenka, J. Huguenard and S. Baccus on this work. All materials are freely distributed and supported by the Deisseroth laboratory (http://www.optogenetics.org). K.D. is supported by the President and Provost of Stanford University, BioX, Bioengineering, and by NIMH, NIDA, CIRM, NSF, and the Keck, McKnight and Coulter Foundations. F.Z. is supported by NINDS, and V.S.S. is supported by a T32 postdoctoral research training fellowship from NIMH.
Author information
Authors and Affiliations
Corresponding author
Supplementary information
Supplementary Information
This file contains Supplementary Methods, Supplementary References, Supplementary Tables 1-2 and Supplementary Figures 1-8 with Legends. (PDF 4122 kb)
Rights and permissions
About this article
Cite this article
Sohal, V., Zhang, F., Yizhar, O. et al. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459, 698â702 (2009). https://doi.org/10.1038/nature07991
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nature07991
This article is cited by
-
Activation of prefrontal parvalbumin interneurons ameliorates working memory deficit even under clinically comparable antipsychotic treatment in a mouse model of schizophrenia
Neuropsychopharmacology (2024)
-
Brain stimulation with 40Â Hz heterochromatic flicker extended beyond red, green, and blue
Scientific Reports (2024)
-
Dopamine neuron degeneration in the Ventral Tegmental Area causes hippocampal hyperexcitability in experimental Alzheimerâs Disease
Molecular Psychiatry (2024)
-
Atypical cortical networks in children at high-genetic risk of psychiatric and neurodevelopmental disorders
Neuropsychopharmacology (2024)
-
Sex dependence of opioid-mediated responses to subanesthetic ketamine in rats
Nature Communications (2024)
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.