Different Fear States Engage Distinct Networks within the Intercalated Cell Clusters of the Amygdala.

Daniela Busti, Raffaella Geracitano, Nigel Whittle, Dalezios Yannis, Miroslawa Manko, Walter Kaufmann, Kurt Saetzler, Nicolas Singewald, Marco Capogna, Francesco Ferraguti

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    86 Citations (Scopus)

    Abstract

    Although extinction-based therapies are among the most effective treatments for anxiety disorders, the neural bases of fear extinction remain still essentially unclear. Recent evidence suggests that the intercalated cell masses of the amygdala (ITCs) are critical structures for fear extinction. However, the neuronal organization of ITCs and how distinct clusters contribute to different fear states are still entirely unknown. Here, by combining whole-cell patch-clamp recordings and biocytin labeling with full anatomical reconstruction of the filled neurons and ultrastructural analysis of their synaptic contacts, we have elucidated the cellular organization and efferent connections of one of the main ITC clusters in mice. Our data showed an unexpected heterogeneity in the axonal pattern of medial paracapsular ITC (Imp) neurons and the presence of three distinct neuronal subtypes. Functionally, we observed that the Imp was preferentially activated during fear expression, whereas extinction training and extinction retrieval activated the main ITC nucleus (IN), as measured by quantifying Zif268 expression. This can be explained by the IPSPs evoked in the IN after Imp stimulation, most likely through the GABAergic monosynaptic innervation of IN neurons by one subtype of Imp cells, namely the medial capsular-projecting (MCp)-Imp neurons. MCp-Imp neurons also target large ITC cells that surround ITC clusters and express the metabotropic glutamate receptor 1alpha. These findings reveal a distinctive participation of ITC clusters to different fear states and the underlying anatomical circuitries, hence shedding new light on ITC networks and providing a novel framework to elucidate their role in fear expression and extinction.
    LanguageEnglish
    Pages5131-5144
    JournalJ Neurosci
    Volume31
    Issue number13
    DOIs
    Publication statusPublished - Mar 2011

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    Amygdala
    Fear
    Neurons
    Inhibitory Postsynaptic Potentials
    Metabotropic Glutamate Receptors
    Anxiety Disorders
    Psychological Extinction

    Cite this

    Busti, D., Geracitano, R., Whittle, N., Yannis, D., Manko, M., Kaufmann, W., ... Ferraguti, F. (2011). Different Fear States Engage Distinct Networks within the Intercalated Cell Clusters of the Amygdala. J Neurosci, 31(13), 5131-5144. https://doi.org/10.1523/JNEUROSCI.6100-10.2011
    Busti, Daniela ; Geracitano, Raffaella ; Whittle, Nigel ; Yannis, Dalezios ; Manko, Miroslawa ; Kaufmann, Walter ; Saetzler, Kurt ; Singewald, Nicolas ; Capogna, Marco ; Ferraguti, Francesco. / Different Fear States Engage Distinct Networks within the Intercalated Cell Clusters of the Amygdala. In: J Neurosci. 2011 ; Vol. 31, No. 13. pp. 5131-5144.
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    abstract = "Although extinction-based therapies are among the most effective treatments for anxiety disorders, the neural bases of fear extinction remain still essentially unclear. Recent evidence suggests that the intercalated cell masses of the amygdala (ITCs) are critical structures for fear extinction. However, the neuronal organization of ITCs and how distinct clusters contribute to different fear states are still entirely unknown. Here, by combining whole-cell patch-clamp recordings and biocytin labeling with full anatomical reconstruction of the filled neurons and ultrastructural analysis of their synaptic contacts, we have elucidated the cellular organization and efferent connections of one of the main ITC clusters in mice. Our data showed an unexpected heterogeneity in the axonal pattern of medial paracapsular ITC (Imp) neurons and the presence of three distinct neuronal subtypes. Functionally, we observed that the Imp was preferentially activated during fear expression, whereas extinction training and extinction retrieval activated the main ITC nucleus (IN), as measured by quantifying Zif268 expression. This can be explained by the IPSPs evoked in the IN after Imp stimulation, most likely through the GABAergic monosynaptic innervation of IN neurons by one subtype of Imp cells, namely the medial capsular-projecting (MCp)-Imp neurons. MCp-Imp neurons also target large ITC cells that surround ITC clusters and express the metabotropic glutamate receptor 1alpha. These findings reveal a distinctive participation of ITC clusters to different fear states and the underlying anatomical circuitries, hence shedding new light on ITC networks and providing a novel framework to elucidate their role in fear expression and extinction.",
    author = "Daniela Busti and Raffaella Geracitano and Nigel Whittle and Dalezios Yannis and Miroslawa Manko and Walter Kaufmann and Kurt Saetzler and Nicolas Singewald and Marco Capogna and Francesco Ferraguti",
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    Busti, D, Geracitano, R, Whittle, N, Yannis, D, Manko, M, Kaufmann, W, Saetzler, K, Singewald, N, Capogna, M & Ferraguti, F 2011, 'Different Fear States Engage Distinct Networks within the Intercalated Cell Clusters of the Amygdala.', J Neurosci, vol. 31, no. 13, pp. 5131-5144. https://doi.org/10.1523/JNEUROSCI.6100-10.2011

    Different Fear States Engage Distinct Networks within the Intercalated Cell Clusters of the Amygdala. / Busti, Daniela; Geracitano, Raffaella; Whittle, Nigel; Yannis, Dalezios; Manko, Miroslawa; Kaufmann, Walter; Saetzler, Kurt; Singewald, Nicolas; Capogna, Marco; Ferraguti, Francesco.

    In: J Neurosci, Vol. 31, No. 13, 03.2011, p. 5131-5144.

    Research output: Contribution to journalArticle

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    T1 - Different Fear States Engage Distinct Networks within the Intercalated Cell Clusters of the Amygdala.

    AU - Busti, Daniela

    AU - Geracitano, Raffaella

    AU - Whittle, Nigel

    AU - Yannis, Dalezios

    AU - Manko, Miroslawa

    AU - Kaufmann, Walter

    AU - Saetzler, Kurt

    AU - Singewald, Nicolas

    AU - Capogna, Marco

    AU - Ferraguti, Francesco

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