Letter | Published:

Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression

Nature volume 505, pages 9296 (02 January 2014) | Download Citation


Synchronization of spiking activity in neuronal networks is a fundamental process that enables the precise transmission of information to drive behavioural responses1,2,3. In cortical areas, synchronization of principal-neuron spiking activity is an effective mechanism for information coding that is regulated by GABA (γ-aminobutyric acid)-ergic interneurons through the generation of neuronal oscillations4,5. Although neuronal synchrony has been demonstrated to be crucial for sensory, motor and cognitive processing6,7,8, it has not been investigated at the level of defined circuits involved in the control of emotional behaviour. Converging evidence indicates that fear behaviour is regulated by the dorsomedial prefrontal cortex9,10,11,12 (dmPFC). This control over fear behaviour relies on the activation of specific prefrontal projections to the basolateral complex of the amygdala (BLA), a structure that encodes associative fear memories13,14,15. However, it remains to be established how the precise temporal control of fear behaviour is achieved at the level of prefrontal circuits. Here we use single-unit recordings and optogenetic manipulations in behaving mice to show that fear expression is causally related to the phasic inhibition of prefrontal parvalbumin interneurons (PVINs). Inhibition of PVIN activity disinhibits prefrontal projection neurons and synchronizes their firing by resetting local theta oscillations, leading to fear expression. Our results identify two complementary neuronal mechanisms mediated by PVINs that precisely coordinate and enhance the neuronal activity of prefrontal projection neurons to drive fear expression.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    Neuronal synchrony: a versatile code for the definition of relations? Neuron 24, 49–65,–111–125 (1999)

  2. 2.

    & Neuronal oscillations in cortical networks. Science 304, 1926–1929 (2004)

  3. 3.

    et al. Modulation of neuronal interactions through neuronal synchronization. Science 316, 1609–1612 (2007)

  4. 4.

    et al. Control of timing, rate and bursts of hippocampal place cells by dendritic and somatic inhibition. Nature Neurosci. 15, 769–775 (2012)

  5. 5.

    , , , & Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature 378, 75–78 (1995)

  6. 6.

    et al. Coherent theta oscillations and reorganization of spike timing in the hippocampal- prefrontal network upon learning. Neuron 66, 921–936 (2010)

  7. 7.

    , & Multiplexing using synchrony in the zebrafish olfactory bulb. Nature Neurosci. 7, 862–871 (2004)

  8. 8.

    , , & Spike synchronization and rate modulation differentially involved in motor cortical function. Science 278, 1950–1953 (1997)

  9. 9.

    , & Sustained conditioned responses in prelimbic prefrontal neurons are correlated with fear expression and extinction failure. J. Neurosci. 29, 8474–8482 (2009)

  10. 10.

    et al. Pavlovian fear memory induced by activation in the anterior cingulate cortex. Mol. Pain 1, 6 (2005)

  11. 11.

    , , & Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. Learn. Mem. 13, 728–733 (2006)

  12. 12.

    & Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears. J. Neurosci. 27, 840–844 (2007)

  13. 13.

    & Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol. Rev. 90, 419–463 (2010)

  14. 14.

    et al. Functional anatomy of neural circuits regulating fear and extinction. Proc. Natl Acad. Sci. USA 109, 17093–17098 (2012)

  15. 15.

    Emotion circuits in the brain. Annu. Rev. Neurosci. 23, 155–184 (2000)

  16. 16.

    , & Distinct firing patterns of identified basket and dendrite-targeting interneurons in the prefrontal cortex during hippocampal theta and local spindle oscillations. J. Neurosci. 29, 9563–9574 (2009)

  17. 17.

    & Perisomatic inhibition. Neuron 56, 33–42 (2007)

  18. 18.

    et al. A novel network of multipolar bursting interneurons generates theta frequency oscillations in neocortex. Neuron 38, 805–817 (2003)

  19. 19.

    , , & Network mechanisms of theta related neuronal activity in hippocampal CA1 pyramidal neurons. Nature Neurosci. 13, 967–972 (2010)

  20. 20.

    & Involvement of GABAergic and cholinergic medial septal neurons in hippocampal theta rhythm. Hippocampus 15, 381–392 (2005)

  21. 21.

    , , , & Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J. Comp. Neurol. 492, 145–177 (2005)

  22. 22.

    , , & Evidence of Pavlovian conditioned fear following electrical stimulation of the periaqueductal grey in the rat. Physiol. Behav. 40, 55–63 (1987)

  23. 23.

    et al. Switching on and off fear by distinct neuronal circuits. Nature 454, 600–606 (2008)

  24. 24.

    , , & Gating of fear in prelimbic cortex by hippocampal and amygdala inputs. Neuron 76, 804–812 (2012)

  25. 25.

    , , , & Influence of the hippocampus on interneurons of the rat prefrontal cortex. Eur. J. Neurosci. 20, 514–524 (2004)

  26. 26.

    , , & Theta reset produces optimal conditions for long-term potentiation. Hippocampus 14, 684–687 (2004)

  27. 27.

    , , & Hippocampal evoked potentials and EEG changes during classical conditioning in the rat. Electroencephalogr. Clin. Neurophysiol. 47, 64–74 (1979)

  28. 28.

    et al. Reset of human neocortical oscillations during a working memory task. Proc. Natl Acad. Sci. USA 100, 7931–7936 (2003)

  29. 29.

    & Amygdala-prefrontal synchronization underlies resistance to extinction of aversive memories. Neuron 75, 133–142 (2012)

  30. 30.

    , & Single-unit activity in the medial prefrontal cortex during immediate and delayed extinction of fear in rats. PLoS ONE 5, e11971 (2010)

Download references


We thank members of the Herry laboratory, K. Benchenane and D. Dupret for comments on the manuscript, K. Deisseroth and E. Boyden for generously sharing material, J. Bacelo, S. Wolff and P. Tovote for technical and computational assistance, the Bordeaux Imaging center of the University of Bordeaux, and C. Poujol and S. Marais for technical assistance with microscopy. This work was supported by grants from the French National Research Agency (ANR-2010-BLAN-1442-01; ANR-10-EQPX-08 OPTOPATH), the European Research Council (ERC) under the European Union’s Seventh Framework Program (FP7/2007-2013)/ERC grant agreement no. 281168, a Fonds AXA pour la recherche doctoral fellowship (J.C.) and the Conseil Regional d’Aquitaine. T.C.M.B is a fellow of Ecole de l’Inserm Liliane Bettencourt-MD-PhD program, France.

Author information


  1. INSERM, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, Bordeaux 33077, France

    • Julien Courtin
    • , Fabrice Chaudun
    • , Robert R. Rozeske
    • , Nikolaos Karalis
    • , Cecilia Gonzalez-Campo
    • , Hélène Wurtz
    • , Thomas C. M. Bienvenu
    •  & Cyril Herry
  2. University of Bordeaux, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, Bordeaux 33077, France

    • Julien Courtin
    • , Fabrice Chaudun
    • , Robert R. Rozeske
    • , Nikolaos Karalis
    • , Cecilia Gonzalez-Campo
    • , Hélène Wurtz
    • , Thomas C. M. Bienvenu
    •  & Cyril Herry
  3. University of Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux F-33000, France

    • Azzedine Abdi
    •  & Jerome Baufreton
  4. CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux F-33000, France

    • Azzedine Abdi
    •  & Jerome Baufreton


  1. Search for Julien Courtin in:

  2. Search for Fabrice Chaudun in:

  3. Search for Robert R. Rozeske in:

  4. Search for Nikolaos Karalis in:

  5. Search for Cecilia Gonzalez-Campo in:

  6. Search for Hélène Wurtz in:

  7. Search for Azzedine Abdi in:

  8. Search for Jerome Baufreton in:

  9. Search for Thomas C. M. Bienvenu in:

  10. Search for Cyril Herry in:


J.C., F.C., R.R.R., N.K., C.G.-C., H.W., A.A., J.B. and T.C.M.B. performed the experiments and analysed the data. J.C. and C.H. designed the experiments and wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Cyril Herry.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Methods and a Supplementary Discussion. The Supplementary Methods contain additional information about the methodology used for in vitro electrophysiology, anatomical analyses, pharmacological inactivation, electrical extracellular stimulation, virus injection and optogenetics and field potential analyses. The Supplementary Discussion discusses the role of PV INs in aversive and appetitive behaviours and the origin and influence of the changes in neuronal activity observed in dmPFC PNs during fear behaviour.

About this article

Publication history







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.